Interleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms

Ohmori, Yoshihiro; Hamilton, Thomas A.

doi:10.1074/jbc.m006227200

Cited by 107Cytokine Signaling Pathways and InteractionsNF-κB Signaling PathwaysGenomics and Chromatin Dynamics

Interleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms

Open access

Ohmori, Yoshihiro, Hamilton, Thomas A.·2000·Journal of Biological Chemistry

DOI 10.1074/jbc.m006227200

Open this paper in CoChat — free account

Abstract

STAT6 mediates interleukin-4 (IL-4)-dependent positive and negative regulation of inflammatory gene expression. In the present report we examined the molecular mechanisms involved in IL-4-induced repression of reporter gene transcription driven by STAT1 and/or NF-kappaB. Transient expression of STAT6 in a STAT6-deficient cell line (HEK 293) conferred sensitivity to IL-4 for STAT6-dependent transcription and for repression of interferon-gamma (IFNgamma)/STAT1- and/or tumor necrosis factor-alpha (TNFalpha)/NF-kappaB-driven reporter gene expression. In cells transfected with a deletion mutant of STAT6 lacking its transactivating domain, IL-4 could not mediate either positive or negative control of reporter gene expression. Overexpression of CREB-binding protein dramatically enhanced IL-4/STAT6-stimulated transcription and overcame IL-4-mediated repression of TNFalpha/NF-kappaB-dependent but not IFNgamma/STAT1-dependent transcription. A single amino acid change in the DNA-binding domain of STAT6 (H415A) selectively reduced the affinity of STAT6 for IL-4-responsive STAT sequence motifs (N4) without affecting the affinity for IFNgamma-responsive (GAS) sequences (N3) and, accordingly, eliminated transcription from an IL-4-responsive promoter. Interestingly, this mutation eliminated IL-4-mediated suppression of reporter gene transcription stimulated by TNFalpha/NF-kappaB but retained nearly full capacity to suppress IFNgamma/STAT1-stimulated transcription. Taken together these results demonstrate that STAT6 mediates suppression of STAT1 and NF-kappaB-dependent transcription by distinct mechanisms. Both processes are dependent upon the STAT6 transactivation domain and may involve sequestration of necessary but different transcriptional coactivator proteins. These two suppressive mechanisms are controlled differentially by the nature of the STAT6 DNA-binding site (i.e. N3 versus N4).

Integrity signals

Registry

Crossref · 10.1074/jbc.m006227200

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

There is cross-talk between the TREM2 and anti-inflammatory IL-4 signaling pathways, in that TREM2 knockdown decreases levels of the STAT6 transcription factor, which is downstream of IL-4.
“Our results suggest that there is cross-talk between the TREM2 and anti-inflammatory IL-4 signaling pathways, in that TREM2 knockdown decreases levels of the STAT6 transcription factor, which is downstream of IL-4 (74).”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [74]

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
Chirgwin, J. M., Przybyla, A., MacDonald, R. J., & Rutter, W. J. (1979) · Biochemistry · doi:10.1021/bi00591a005 · Cited by 21,725 · see citing works
Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262 · see citing works
TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties
Mosmann, T. R., & Coffman, R. L. (1989) · Annual Review of Immunology · doi:10.1146/annurev.iy.07.040189.001045 · Cited by 7,692 · see citing works
Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080 · see citing works
Functional diversity of helper T lymphocytes
Abbas, A. K., MURPHY, K. M. M., & Sher, A. (1996) · Nature · doi:10.1038/383787a0 · Cited by 4,383 · see citing works
A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors
Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S.-C., Heyman, R. A., Rose, D. W., Glass, C. K., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81118-6 · Cited by 2,150 · see citing works
Maximal activation of transcription by statl and stat3 requires both tyrosine and serine phosphorylation
Wen, Z., Zhong, Z., & Darnell, J. E. (1995) · Cell · doi:10.1016/0092-8674(95)90311-9 · Cited by 1,974 · see citing works
TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway
Schindler, C., & Darnell, J. E. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003201 · Cited by 1,808 · see citing works
The IL-4 receptor: signaling mechanisms and biologic functions
Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.701 · Cited by 1,545 · see citing works
Cytokines Induce the Development of Functionally Heterogeneous T Helper Cell Subsets
O’Garra, A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80533-6 · Cited by 1,535 · see citing works
A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A
Yang, X., Ogryzko, V. V., Nishikawa, J., Howard, B. H., & Nakatani, Y. (1996) · Nature · doi:10.1038/382319a0 · Cited by 1,473 · see citing works
The Molecular Cell Biology of Interferon-gamma and its Receptor
Farrar, M. A., & Schreiber, R. D. (1993) · Annual Review of Immunology · doi:10.1146/annurev.iy.11.040193.003035 · Cited by 1,345 · see citing works
CYTOKINES: COORDINATORS OF IMMUNE AND INFLAMMATORY RESPONSES
Arai, K., Lee, F., Miyajima, A., Miyatake, S., Arai, N., & Yokota, T. (1990) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.59.070190.004031 · Cited by 1,318 · see citing works
The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function
Torchia, J., Rose, D. W., Inostroza, J. A., Kamei, Y., Westin, S. K., Glass, C. K., & Rosenfeld, M. G. (1997) · Nature · doi:10.1038/42652 · Cited by 1,283 · see citing works
Regulation of Transcription by a Protein Methyltransferase
Chen, D., Ma, H., Hong, H., Koh, S. S., Huang, S., Schurter, B. T., Aswad, D. W., & Stallcup, M. R. (1999) · Science · doi:10.1126/science.284.5423.2174 · Cited by 1,214 · see citing works
Fundamental Immunology
Anderson, P. C. (1999) · JAMA · doi:10.1001/jama.281.24.2351 · Cited by 1,013 · see citing works
Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements
Miyamoto, M., Fujita, T., Kimura, Y., Maruyama, M., Harada, H., Sudo, Y., Miyata, T., & Taniguchi, T. (1988) · Cell · doi:10.1016/s0092-8674(88)91307-4 · Cited by 977 · see citing works
An Interleukin-4-Induced Transcription Factor: IL-4 Stat
Hou, J., Schindler, U., Henzel, W. J., Ho, T. C., Brasseur, M., & McKnight, S. L. (1994) · Science · doi:10.1126/science.8085155 · Cited by 855 · see citing works
CREB-binding protein/p300 are transcriptional coactivators of p65
Gerritsen, M. E., Williams, A. J., Neish, A. S., Moore, S., Shi, Y., & Collins, T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.2927 · Cited by 811 · see citing works
Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein.
Shuai, K., Schindler, C., Prezioso, V., & Darnell, J. (1992) · Science · doi:10.1126/science.1281555 · Cited by 784 · see citing works
Two contact regions between Stat1 and CBP/p300 in interferon γ signaling
Zhang, J. J., Vinkemeier, U., Gu, W., Chakravarti, D., Horvath, C. M., & Darnell, J. E., Jr. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.26.15092 · Cited by 485 · see citing works
Genetic isolation of ADA2: A potential transcriptional adaptor required for function of certain acidic activation domains
Berger, S. L., Piña, B., Silverman, N., Marcus, G. A., Agapite, J., Regier, J. L., Triezenberg, S. J., & Guarente, L. (1992) · Cell · doi:10.1016/0092-8674(92)90100-q · Cited by 435 · see citing works
Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300
Horvai, A., Xu, L., Korzus, E., Brard, G., Kalafus, D., Mullen, T.-M., Rose, D. W., Rosenfeld, M. G., & Glass, C. K. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1074 · Cited by 422 · see citing works
IL-4 down-regulates IL-1 and TNF gene expression in human monocytes.
Essner, R., Rhoades, K. L., McBride, W. H., Morton, D., & Economou, J. S. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.142.11.3857 · Cited by 416 · see citing works
Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity.
Seidel, H. M., Milocco, L. H., Lamb, P., Darnell, J. E., Stein, R. B., & Rosen, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.3041 · Cited by 415 · see citing works
Synergy between Interferon-γ and Tumor Necrosis Factor-α in Transcriptional Activation Is Mediated by Cooperation between Signal Transducer and Activator of Transcription 1 and Nuclear Factor κB
Ohmori, Y., Schreiber, R. D., & Hamilton, T. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.23.14899 · Cited by 413 · see citing works
Cloning of Murine Stat6 and Human Stat6, Stat Proteins That Are Tyrosine Phosphorylated in Responses to IL-4 and IL-3 but Are Not Required for Mitogenesis
Quelle, F. W., Shimoda, K., Thierfelder, W. E., Fischer, C. D., Kim, A., Ruben, S. M., Cleveland, J. L., Pierce, J. H., Keegan, A. D., Nelms, K. A., et al. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.6.3336 · Cited by 324 · see citing works
Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist.
Vannier, E. G., Miller, L. C., & Dinarello, C. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.9.4076 · Cited by 321 · see citing works
Regulation of the production of the RANTES chemokine by endothelial cells. Synergistic induction by IFN-gamma plus TNF-alpha and inhibition by IL-4 and IL-13.
Marfaing‐Koka, A., Devergne, O., Gorgone, G., Portier, A., Schall, T. J., Galanaud, P., & Émilie, D. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.4.1870 · Cited by 305 · see citing works
Nuclear Integration of Glucocorticoid Receptor and Nuclear Factor-κB Signaling by CREB-binding Protein and Steroid Receptor Coactivator-1
Sheppard, K.-A., Phelps, K. M., Williams, A. J., Thanos, D., Glass, C. K., Rosenfeld, M. G., Gerritsen, M. E., & Collins, T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29291 · Cited by 305 · see citing works
Protein synthesis inhibitors differentially superinduce c‐fos and c‐jun by three distinct mechanisms: lack of evidence for labile repressors.
Edwards, D. R., & Mahadevan, L. C. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05306.x · Cited by 280 · see citing works
Requirements for Interleukin-4-Induced Gene Expression and Functional Characterization of Stat6
Mikita, T., Campbell, D., Wu, P., Williamson, K., & Schindler, U. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.10.5811 · Cited by 271 · see citing works
A Novel Interferon-Inducible Domain: Structural and Functional Analysis of the Human Interferon Regulatory Factor 1 Gene Promoter
Sims, S. H., Cha, Y., Romine, M. F., Gao, P. Q., Gottlieb, K., & Deisseroth, A. B. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.690 · Cited by 262 · see citing works
Requirement of Tyrosine Phosphorylation for Rapid Activation of a DNA Binding Factor by IL-4
Kotanides, H., & Reich, N. C. (1993) · Science · doi:10.1126/science.7694370 · Cited by 256 · see citing works
Components of a stat recognition code: Evidence for two layers of molecular selectivity
Schindler, U., Wu, P., Rothe, M., Brasseur, M., & McKnight, S. L. (1995) · Immunity · doi:10.1016/1074-7613(95)90013-6 · Cited by 246 · see citing works
Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages
Bogdan, C., Yoram Vodovotz, B., Paik, J., Xie, Q. W., & Nathan, C. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.55.2.227 · Cited by 231 · see citing works
Interaction of Stat6 and NF-κB: Direct Association and Synergistic Activation of Interleukin-4-Induced Transcription
Shen, C.-H., & Stavnezer, J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3395 · Cited by 209 · see citing works
Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF-IL-4, a C/EBP family member and NF-kappa B/p50.
Delphin, S. A., & Stavnezer, J. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.1.181 · Cited by 201 · see citing works
Proteasome‐mediated degradation of transcriptional activators correlates with activation domain potency in vivo
Molinari, E., Gilman, M. Z., & Natesan, S. (1999) · The EMBO Journal · doi:10.1093/emboj/18.22.6439 · Cited by 185 · see citing works
STF‐IL‐4: a novel IL‐4‐induced signal transducing factor.
Schindler, C., Kashleva, H., Pernis, A. B., Pine, R. I., & Rothman, P. B. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06388.x · Cited by 180 · see citing works
Convergence of TNF and IFN signalling pathways through synergistic induction of IRF-1/ISGF-2 is mediated by a composite GAS/ B promoter element
Pine, R. I. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.21.4346 · Cited by 164 · see citing works
IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages
Ohmori, Y., & Hamilton, T. A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.11.5474 · Cited by 161 · see citing works
Interleukin-4 Suppression of Tumor Necrosis Factor α-stimulated E-selectin Gene Transcription Is Mediated by STAT6 Antagonism of NF-κB
Bennett, B. L., Cruz, R., Lacson, R., & Manning, A. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.15.10212 · Cited by 147 · see citing works
IL-4 decreases Fc gamma R membrane expression and Fc gamma R-mediated cytotoxic activity of human monocytes.
Velde, A. A. T., Huijbens, R. J. F., de Vries, J. E., & Figdor, C. G. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.8.3046 · Cited by 130 · see citing works
p300/CBP is required for transcriptional induction by interleukin-4 and interacts with Stat6
Gingras, S., Simard, J., Groner, B., & Pfitzner, E. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.13.2722 · Cited by 129 · see citing works
Signaling by the Cytokine Receptor Superfamilya
Ihle, J. N., Thierfelder, W. E., Teglund, S., STRAVAPODIS, D., Wang, D., Feng, J., & Parganas, E. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb11157.x · Cited by 118 · see citing works
Interleukin-4-induced STAT6 Recognizes and Activates a Target Site in the Promoter of the Interleukin-4 Receptor Gene
Kotanides, H., & Reich, N. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.41.25555 · Cited by 109 · see citing works
IL-4 suppresses cytokine gene expression induced by IFN-gamma and/or IL-2 in murine peritoneal macrophages
Gautam, S., Tebo, J. M., & Hamilton, T. A. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.6.1725 · Cited by 108 · see citing works
IL-1 expression in human monocytes is transcriptionally and posttranscriptionally regulated by IL-4
Donnelly, R. P., Fenton, M. J., Kaufman, J. D., & Gerrard, T. L. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.10.3431 · Cited by 102 · see citing works
STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages
Ohmori, Y., & Hamilton, T. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.29202 · Cited by 102 · see citing works
Differential regulation of IL-6 gene transcription and expression by IL-4 and IL-10 in human monocytic cell lines
Takeshita, S., Gage, J. R., Kishimoto, T., Vredevoe, D. L., & Martı́nez-Maza, O. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.7.2591 · Cited by 98 · see citing works
IFN-gamma selectively inhibits lipopolysaccharide-inducible JE/monocyte chemoattractant protein-1 and KC/GRO/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages.
Ohmori, Y., & Hamilton, T. A. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.5.2204 · Cited by 97 · see citing works
Tissue-specific regulation of IL-6 production by IL-4. Differential effects of IL-4 on nuclear factor-kappa B activity in monocytes and fibroblasts.
Donnelly, R. P., Crofford, L. J., Freeman, S. L., Buras, J. A., Remmers, E. F., Wilder, R. L., & Fenton, M. J. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.10.5603 · Cited by 90 · see citing works
IL-4-induced expression of the IL-1 receptor antagonist gene is mediated by STAT6
Ohmori, Y., Smith, M. F., & Hamilton, T. A. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.2058 · Cited by 84 · see citing works
Stat5b Inhibits NFκB-Mediated Signaling
Luo, G., & Yu‐Lee, L. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.1.0399 · Cited by 76 · see citing works
Cooperation of the Transcriptional Coactivators CBP and p300 with Stat6
McDonald, C., & Reich, N. C. (1999) · Journal of Interferon & Cytokine Research · doi:10.1089/107999099313550 · Cited by 74 · see citing works
Interleukin-4 Down-regulates Both Forms of Tumor Necrosis Factor Receptor and Receptor-mediated Apoptosis, NF-κB, AP-1, and c-Jun N-Terminal Kinase
Manna, S. K., & Aggarwal, B. B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.50.33333 · Cited by 70 · see citing works
Synergistic activation of the germline epsilon promoter mediated by Stat6 and C/EBP beta.
Mikita, T., Kurama, M., & Schindler, U. (1998) · PubMed · Cited by 62 · see citing works
Synergistic Activation of the Germline ε Promoter Mediated by Stat6 and C/EBPβ
Mikita, T., Kurama, M., & Schindler, U. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.4.1822 · Cited by 58 · see citing works
IL-4 attenuates the transcriptional activation of both IFN-alpha and IFN-gamma-induced cellular gene expression in monocytes and monocytic cell lines
Larner, A. C., Petricoin, E. F., Nakagawa, Y., & Finbloom, D. S. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.5.1944 · Cited by 56 · see citing works
Stat5b Inhibits NF B-Mediated Signaling
Luo, G. (2000) · Molecular Endocrinology · doi:10.1210/me.14.1.114 · Cited by 56 · see citing works
Protein Synthesis Inhibitors Exhibit a Nonspecific Effect on Phenobarbital-inducible Cytochome P450 Gene Expression in Primary Rat Hepatocytes
Sidhu, J. S., & Omiecinski, C. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.8.4769 · Cited by 55 · see citing works
Interleukin-4 inhibits the lipopolysaccharide-induced expression of c- jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes
Dokter, W. H. A., Esselink, M., Halie, M., & Vellenga, E. (1993) · Blood · doi:10.1182/blood.v81.2.337.337 · Cited by 53 · see citing works
Regulation of macrophage gene expression by T-cell-derived lymphokines.
Ohmori, Y., & Hamilton, T. A. (1994) · Pharmacology and Therapeutics · doi:10.1016/0163-7258(94)90026-4 · Cited by 46 · see citing works
Kappa B binding activity in a murine macrophage-like cell line. Sequence-specific differences in kappa B binding and transcriptional activation functions
Ohmori, Y., Tebo, J. M., Nedospasov, S. A., & Hamilton, T. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32495-x · Cited by 36 · see citing works
Mechanisms of IL-4-mediated suppression of IP-10 gene expression in murine macrophages.
Deng, W., Ohmori, Y., & Hamilton, T. A. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.5.2130 · Cited by 36 · see citing works
Paired Stat6 C-Terminal Transcription Activation Domains Required Both for Inhibition of an IFN-Responsive Promoter and Trans- Activation
Goenka, S., Youn, J., Dzurek, L. M., Schindler, U., Yu‐Lee, L., & Boothby, M. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.9.4663 · Cited by 33 · see citing works
11–4 Decreases IFN‐γ‐Induced Endothelial ICAM‐1 Expression by a Transcriptional Mechanism
Renkonen, R., Mattila, P., Majuri, M., Paavonen, T., & Silvennoinen, O. (1992) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1992.tb03251.x · Cited by 32 · see citing works

Flagged first, then by citations

Sorted by citations

Cytokine Milieu of Atopic Dermatitis, as Compared to Psoriasis, Skin Prevents Induction of Innate Immune Response Genes
Nomura, I., Goleva, E., Howell, M. D., Hamid, Q., Ong, P. Y., Hall, C. F., Darst, M. A., Gao, B., Boguniewicz, M., Travers, J. B., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.6.3262 · Cited by 731 · see citing works
Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein
Rosowski, E. E., Lu, D. Y., Julien, L., Rodda, L. B., Gaiser, R. A., Jensen, K. D. C., & Saeij, J. P. J. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100717 · Cited by 418 · see citing works
Cytokine Milieu of Atopic Dermatitis Skin Subverts the Innate Immune Response to Vaccinia Virus
Howell, M. D., Gallo, R. L., Boguniewicz, M., Jones, J. F., Wong, C., Streib, J. E., & Leung, D. Y. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.02.006 · Cited by 335 · see citing works
Signaling mechanisms, interaction partners, and target genes of STAT6
Hebenstreit, D., Wirnsberger, G., Horejs‐Hoeck, J., & Duschl, A. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.01.004 · Cited by 310 · see citing works
Systematic investigation of cytokine signaling activity at the tissue and single-cell levels
Jiang, P., Zhang, Y., Ru, B., Yang, Y.-A., Vu, T., Paul, R., Mirza, A. M., Altan-Bonnet, G. Y., Liu, L., Ruppin, E., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01274-5 · Cited by 243 · see citing works
Inhibition of IFN-γ-Induced Class II Transactivator Expression by a 19-kDa Lipoprotein from Mycobacterium tuberculosis : A Potential Mechanism for Immune Evasion
Pai, R. K., Convery, M., Hamilton, T. A., Boom, W. H., & Harding, C. V. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.175 · Cited by 246 · see citing works
Toxoplasma Rhoptry Protein 16 (ROP16) Subverts Host Function by Direct Tyrosine Phosphorylation of STAT6
Ong, Y.-C., Reese, M. L., & Boothroyd, J. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.112359 · Cited by 233 · see citing works
<i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions
Liu, W., Taso, O., Wang, R., Bayram, S., Graham, A. C., Garcia-Reitboeck, P., Mallach, A., Andrews, W. D., Piers, T. M., Botia, J. A., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa209 · Cited by 214 · see citing works
“Our results suggest that there is cross-talk between the TREM2 and anti-inflammatory IL4 signaling pathways, in that TREM2 knockdown decreases levels of the STAT6 transcription factor, which is downstream of IL4 (Ohmori and Hamilton 2000).”
Background
Mechanism of HBD-3 deficiency in atopic dermatitis
Howell, M. D., Boguniewicz, M., Pastore, S., Novak, N., Bieber, T., Girolomoni, G., & Leung, D. Y. M. (2006) · Clinical Immunology · doi:10.1016/j.clim.2006.08.008 · Cited by 208 · see citing works
Regulation of macrophage polarization and plasticity by complex activation signals
Smith, T. D., Tse, M. J., Read, E. L., & Liu, W. F. (2016) · Integrative Biology · doi:10.1039/c6ib00105j · Cited by 196 · see citing works
IL-4 and IL-13 Negatively Regulate TNF-α- and IFN-γ-Induced β-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3
Albanesi, C., Fairchild, H. R., Madonna, S., Scarponi, C., Pità, O. D., Leung, D. Y. M., & Howell, M. D. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.2.984 · Cited by 194 · see citing works
Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter
Reese, T. A., Wakeman, B. S., Choi, H. S., Hufford, M. M., Huang, S. C., Zhang, X., Buck, M. D., Jezewski, A. J., Kambal, A., Liu, C., et al. (2014) · Science · doi:10.1126/science.1254517 · Cited by 186 · see citing works
Regulation of μ-Opioid Receptor Gene Transcription by Interleukin-4 and Influence of an Allelic Variation within a STAT6 Transcription Factor Binding Site
Kraus, J., Börner, C., Giannini, E., Hickfang, K., Braun, H., Mayer, P. E., Hoehe, M. R., Ambrosch, A., König, W., & Höllt, V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107543200 · Cited by 166 · see citing works
Activation of the STAT pathway in acute lung injury
Severgnini, M., Takahashi, S., Rozo, L., Homer, R., Kuhn, C., Jhung, J. W., Perides, G., Steer, M. L., Hassoun, P. M., Fanburg, B. L., et al. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00349.2003 · Cited by 163 · see citing works
Genome-wide Profiling of Interleukin-4 and STAT6 Transcription Factor Regulation of Human Th2 Cell Programming
Elo, L. L., Järvenpää, H., Tuomela, S., Raghav, S. K., Ahlfors, H., Laurila, K., Gupta, B., Lund, R., Tahvanainen, J., Hawkins, R. D., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.011 · Cited by 155 · see citing works
Microglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1/6 pathway
Qin, C., Liu, Q., Hu, Z.-W., Zhou, L., Shang, K., Bosco, D. B., Wu, L., Tian, D., & Wang, W. (2018) · Theranostics · doi:10.7150/thno.27882 · Cited by 131 · see citing works
Allergic Airway Inflammation Inhibits Pulmonary Antibacterial Host Defense
Beißwenger, C., Kändler, K., Hess, C., Garn, H., Felgentreff, K., Wegmann, M., Renz, H. E., Vogelmeier, C. F., & Bals, R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.3.1833 · Cited by 122 · see citing works
Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor
Goenka, S., & Boothby, M. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506981103 · Cited by 108 · see citing works
Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes
Chen, Z. J., Lund, R., Aittokallio, T. A., Kosonen, M., Nevalainen, O., & Lahesmaa, R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.7.3627 · Cited by 107 · see citing works
The Transcriptional Coactivator CREB-binding Protein Cooperates with STAT1 and NF-κB for Synergistic Transcriptional Activation of the CXC Ligand 9/Monokine Induced by Interferon-γ Gene
Hiroi, M., & Ohmori, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204544200 · Cited by 106 · see citing works
Induction of macrophage insulin-like growth factor-I expression by the Th2 cytokines IL-4 and IL-13
Wynes, M. W., & Riches, D. W. H. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.7.3550 · Cited by 105 · see citing works
Regulation of Chemokine Expression by Antiinflammatory Cytokines
Hamilton, T. A., Ohmori, Y., & Tebo, J. M. (2002) · Immunologic Research · doi:10.1385/ir:25:3:229 · Cited by 90 · see citing works
Interaction between pro-inflammatory and anti-inflammatory cytokines in insulin-producing cells
Souza, K. L. A., Gurgul-Convey, E., Elsner, M., & Lenzen, S. (2008) · Journal of Endocrinology · doi:10.1677/joe-07-0638 · Cited by 89 · see citing works
The anti‐inflammatory effects of interleukin‐4 are not mediated by suppressor of cytokine signalling‐1 (SOCS1)
Woodward, E., Prêle, C. M., Nicholson, S. E., Kolesnik, T. B., & Hart, P. H. (2010) · Immunology · doi:10.1111/j.1365-2567.2010.03281.x · Cited by 82 · see citing works
Untitled work
S., P. A. (2006) · doi:10.4049/jimmunol.176.7.4385 · Cited by 80 · see citing works
IL-4 Pretreatment Selectively Enhances Cytokine and Chemokine Production in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages
Major, J. A., Fletcher, J. E., & Hamilton, T. A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.5.2456 · Cited by 80 · see citing works
NF-κB signalling is inhibited by glucocorticoid receptor and STAT6 via distinct mechanisms
Nelson, G., Wilde, G. J. C., Spiller, D. G., Kennedy, S. M., Ray, D. W., Sullivan, E., Unitt, J. F., & White, M. (2003) · Journal of Cell Science · doi:10.1242/jcs.00461 · Cited by 78 · see citing works
The adenylyl cyclase-cAMP system suppresses TARC/CCL17 and MDC/CCL22 production through p38 MAPK and NF-κB in HaCaT keratinocytes
Qi, X., Kim, D.-H., Yoon, Y., Li, J., Song, S.-B., Jin, D., Huang, X., Teng, Y., & Lee, K. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.03.018 · Cited by 77 · see citing works
An Altered Cellular Response to Interferon and Up-Regulation of Interleukin-8 Induced by the Hepatitis C Viral Protein NS5A Uncovered by Microarray Analysis
Girard, S., Shalhoub, P., Lescure, P., Sabile, A., Misek, D. E., Hanash, S., Bréchot, C., & Beretta, L. (2002) · Virology · doi:10.1006/viro.2002.1373 · Cited by 72 · see citing works
Cytokine Cascades and the Hepatic Inflammatory Response to Ischemia and Reperfusion
Okaya, T., & Lentsch, A. B. (2003) · Journal of Investigative Surgery · doi:10.1080/08941930390205782 · Cited by 71 · see citing works
Structural basis for DNA recognition by STAT6
Li, J., Rodriguez, J. P., Niu, F., Pu, M., Wang, J., Hung, L., Shao, Q., Zhu, Y., Ding, W., Liu, Y., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1611228113 · Cited by 70 · see citing works
Insights into teleost interferon-gamma biology: An update
Pereiro, P., Figueras, A. J., & Novoa, B. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.04.002 · Cited by 69 · see citing works
Cutting Edge: Induction of the Antigen-Processing Enzyme IFN-γ-Inducible Lysosomal Thiol Reductase in Melanoma Cells Is STAT1-Dependent but CIITA-Independent
O’Donnell, P. W., Haque, A., Klemsz, M. J., Kaplan, M. H., & Blum, J. S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.731 · Cited by 69 · see citing works
Human Osteoarthritic Cartilage Shows Reduced In Vivo Expression of IL-4, a Chondroprotective Cytokine that Differentially Modulates IL-1β-Stimulated Production of Chemokines and Matrix-Degrading Enzymes In Vitro
Assirelli, E., Pulsatelli, L., Dolzani, P., Platano, D., Olivotto, E., Filardo, G., Trisolino, G., Facchini, A., Borzì, R., & Meliconi, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096925 · Cited by 65 · see citing works
Interleukin-4 induction of the CC chemokine TARC (CCL17) in murine macrophages is mediated by multiple STAT6 sites in the TARC gene promoter
Liddiard, K., Welch, J. S., Lozach, J., Heinz, S., Glass, C. K., & Greaves, D. R. (2006) · BMC Molecular Biology · doi:10.1186/1471-2199-7-45 · Cited by 63 · see citing works
STAT4 and STAT6 regulate systemic inflammation and protect against lethal endotoxemia
Lentsch, A. B., Kato, A., Davis, B., Wang, W., Chao, C., & Edwards, M. J. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113763 · Cited by 63 · see citing works
Induction of unique macrophage subset by simultaneous stimulation with LPS and IL-4
Ishida, K., Nagatake, T., Saika, A., Kawai, S., Node, E., Hosomi, K., & Kunisawa, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1111729 · Cited by 63 · see citing works
Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity
Ruas, L. P., Bernardes, E. S., Fermino, M. L., de Oliveira, L. L., Hsu, D. K., Liu, F., Chammas, R. J., & Roque‐Barreira, M. C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004519 · Cited by 60 · see citing works
Constitutive nuclear factor κB activity is required to elicit interferon-γ-induced expression of chemokine CXC ligand 9 (CXCL9) and CXCL10 in human tumour cell lines
Hiroi, M., & Ohmori, Y. (2003) · Biochemical Journal · doi:10.1042/bj20030842 · Cited by 56 · see citing works
The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections
Howell, M. D., Gao, P., Kim, B. E., Lesley, L. J., Streib, J. E., Taylor, P. A., Zaccaro, D. J., Boguniewicz, M., Beck, L. A., Hanifin, J. M., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.06.003 · Cited by 54 · see citing works
Molecular mechanisms of lipopolysaccharide-induced cyclooxygenase-2 expression in human neutrophils: involvement of the mitogen-activated protein kinase pathway and regulation by anti-inflammatory cytokines
Nagano, S. (2002) · International Immunology · doi:10.1093/intimm/dxf038 · Cited by 54 · see citing works
NF-κB Signaling Participates in Both RANKL- and IL-4–Induced Macrophage Fusion: Receptor Cross-Talk Leads to Alterations in NF-κB Pathways
Yu, M., Qi, X., Moreno, J. L., Färber, D. L., & Keegan, A. D. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002628 · Cited by 53 · see citing works
Interferon-γ Modulates Prolactin and Tissue Factor Expression in Differentiating Human Endometrial Stromal Cells1
Christian, M., Marangos, P., Mak, I., McVey, J. H., Barker, F. G., WHITE, J. O., & Brosens, J. J. (2001) · Endocrinology · doi:10.1210/endo.142.7.8231 · Cited by 53 · see citing works
STAT6 and STAT1 are essential antagonistic regulators of cell survival in classical Hodgkin lymphoma cell line
Baus, D., Nonnenmacher, F., Jankowski, S., Döring, C., Bräutigam, C., Frank, M., Hansmann, M.-L., & Pfitzner, E. (2009) · Leukemia · doi:10.1038/leu.2009.103 · Cited by 52 · see citing works
Roles of programmed death protein 1/programmed death-ligand 1 in secondary brain injury after intracerebral hemorrhage in rats: selective modulation of microglia polarization to anti-inflammatory phenotype
Wu, J., Sun, L., Li, H., Shen, H., Zhai, W., Yu, Z., & Chen, G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0790-0 · Cited by 49 · see citing works
Differential Effects of TNF-α and IFN-γ on Gene Transcription Mediated by NF-κB-Stat1 Interactions
Ganster, R. W., Guo, Z., Shao, L., & Geller, D. A. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.707 · Cited by 48 · see citing works
IL-4 Suppresses Dendritic Cell Response to Type I Interferons
Sriram, U., Biswas, C., Behrens, E. M., Dinnall, J.-A., Shivers, D. K., Monestier, M., Argon, Y., & Gallucci, S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6446 · Cited by 44 · see citing works
Interleukin-4 and Transforming Growth Factor β Have Opposing Regulatory Effects on Gamma Interferon-Mediated Inhibition ofCryptosporidium parvumReproduction
Lean, I.-S., McDonald, S. A. C., Bajaj‐Elliott, M., Pollok, R., Farthing, M. J. G., & McDonald, V. (2003) · Infection and Immunity · doi:10.1128/iai.71.8.4580-4585.2003 · Cited by 44 · see citing works
STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases
Tolomeo, M., & Cascio, A. (2024) · International Reviews of Immunology · doi:10.1080/08830185.2024.2395274 · Cited by 43 · see citing works
Endogenous IL-13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury
Kato, A., Okaya, T., & Lentsch, A. B. (2003) · Hepatology · doi:10.1053/jhep.2003.50075 · Cited by 40 · see citing works
Helminth–virus interactions: determinants of coinfection outcomes
Desai, P., Diamond, M., & Thackray, L. B. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1961202 · Cited by 39 · see citing works
IgE and IL‐33−mediated triggering of human basophils inhibits TLR4−induced monocyte activation
Rivellese, F., Suurmond, J., de Paulis, A., Marone, G., Huizinga, T. W. J., & Toes, R. E. M. (2014) · European Journal of Immunology · doi:10.1002/eji.201444731 · Cited by 37 · see citing works
Interleukin‐4 downregulates TNFα‐induced IL‐8 production in keratinocytes
Raingeaud, J., & Pierre, J. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.06.019 · Cited by 36 · see citing works
Cellular and Molecular Mechanisms Underpinning Macrophage Activation during Remyelination
Lloyd, A. F., & Miron, V. E. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00060 · Cited by 35 · see citing works
Interleukin‐4 and interleukin‐10 modulate nuclear factor κB activity and nitric oxide synthase‐2 expression in Theiler's virus‐infected brain astrocytes
Molina‐Holgado, E., Arévalo‐Martín, Á., Castrillo, A., Boscá, L., Vela, J. M., & Guaza, C. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00925.x · Cited by 35 · see citing works
Recombinant human brain natriuretic peptide ameliorates trauma-induced acute lung injury via inhibiting JAK/STAT signaling pathway in rats
Song, Z., Zhao, X., Gao, Y., Liu, M., Hou, M., Jin, H., & Cui, Y. (2015) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0000000000000602 · Cited by 33 · see citing works
Anti-Inflammatory Cytokine Interleukin-4 Inhibits Inducible Nitric Oxide Synthase Gene Expression in the Mouse Macrophage Cell Line RAW264.7 through the Repression of Octamer-Dependent Transcription
Hiroi, M., Sakaeda, Y., Yamaguchi, H., & Ohmori, Y. (2013) · Mediators of Inflammation · doi:10.1155/2013/369693 · Cited by 29 · see citing works
Rhinovirus-Induced CCL17 and CCL22 in Asthma Exacerbations and Differential Regulation by STAT6
Williams, T. C., Jackson, D. J., Maltby, S., Walton, R. P., Ching, Y.-M., Glanville, N., Singanayagam, A., Brewins, J. J., Clarke, D. L., Hirsman, A. G., et al. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0011oc · Cited by 27 · see citing works
The Transcription Factor p63 Is a Direct Effector of IL-4– and IL-13–Mediated Repression of Keratinocyte Differentiation
Brauweiler, A. M., Leung, D. Y. M., & Goleva, E. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.09.009 · Cited by 26 · see citing works
Influence of Ce3+ Substitution on Antimicrobial and Antibiofilm Properties of ZnCexFe2−xO4 Nanoparticles (X = 0.0, 0.02, 0.04, 0.06, and 0.08) Conjugated with Ebselen and Its Role Subsidised with γ-Radiation in Mitigating Human TNBC and Colorectal Adenocarcinoma Proliferation In Vitro
Abdel-Rafei, M. K., Thabet, N. M., Maksoud, M. I. A. A., Elkodous, M. A., Kawamura, G., Matsuda, A., Ashour, A., El-Batal, A. I., & El-Sayyad, G. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221810171 · Cited by 26 · see citing works
A20 is a master switch of IL-33 signaling in macrophages and determines IL-33–induced lung immunity
Holgado, A., Liu, Z., Aidarova, A., Mueller, C., Haegman, M., Driege, Y., Kreike, M., Scott, C. L., Afonina, I. S., & Beyaert, R. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.02.026 · Cited by 25 · see citing works
Further Pharmacological Evidence of Nuclear Factor-κB Pathway Involvement in Bradykinin B1 Receptor-Sensitized Responses in Human Umbilical Vein
Sardi, S. P., Rey‐Ares, V., Lereis, V. P., Serrano, S. A., & Rothlin, R. P. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.301.3.975 · Cited by 25 · see citing works
Interleukin-4 and interleukin-13 inhibit the expression of leukemia inhibitory factor and interleukin-11 in fibroblasts
de Souza, P. C., Palmqvist, P., Lundberg, P., Lundgren, I., Hänström, L., de Souza, J. A. C., Conaway, H. H., & Lerner, U. H. (2011) · Molecular Immunology · doi:10.1016/j.molimm.2011.10.009 · Cited by 24 · see citing works
Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression
Fukuda, M., Kusama, K., & Sakashita, H. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-376 · Cited by 24 · see citing works
IL-4 Suppresses the Responses to TLR7 and TLR9 Stimulation and Increases the Permissiveness to Retroviral Infection of Murine Conventional Dendritic Cells
Sriram, U., Xu, J., Chain, R. W., Varghese, L., Chakhtoura, M., Bennett, H., Zoltick, P. W., & Gallucci, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087668 · Cited by 23 · see citing works
Monocyte and Alveolar Macrophage Skewing Is Associated with the Development of Pulmonary Arterial Hypertension in a Primate Model of HIV Infection
Schweitzer, F., Tarantelli, R., Rayens, E. A., Kling, H. M., Mattila, J. T., & Norris, K. A. (2018) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2018.0132 · Cited by 22 · see citing works
Interaction of allergic airway inflammation and innate immunity: hygiene and beyond
Beißwenger, C., & Bals, R. (2008) · Journal of Occupational Medicine and Toxicology · doi:10.1186/1745-6673-3-s1-s3 · Cited by 22 · see citing works
Differential Roles of C-terminal Activation Motifs in the Establishment of Stat6 Transcriptional Specificity
Goenka, S., Marlar, C. A., Schindler, U., & Boothby, M. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305854200 · Cited by 21 · see citing works
Chemokines in Cartilage Regeneration and Degradation: New Insights
Edderkaoui, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010381 · Cited by 20 · see citing works
Interleukin 6 −174G>C polymorphism and cancer risk: Meta-analysis reveals a site dependent differential influence in Ancestral North Indians
Joshi, N. N., Kannan, S., Kotian, N., Bhat, S., Kale, M., & Hake, S. S. (2014) · Human Immunology · doi:10.1016/j.humimm.2014.06.018 · Cited by 19 · see citing works
Regulatory Mechanisms of Injury and Repair after Hepatic Ischemia/Reperfusion
Lentsch, A. B. (2012) · Scientifica · doi:10.6064/2012/513192 · Cited by 18 · see citing works
Expression of interleukin 4 receptors in bronchial asthma patients who underwent specific immunotherapy
Kowal, K., Osada, J., Zukowski, S., Dąbrowska, M., DuBuske, L. M., & Bodzenta‐Łukaszyk, A. (2004) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)61449-4 · Cited by 18 · see citing works
Insights on TAM Formation from a Boolean Model of Macrophage Polarization Based on In Vitro Studies
Marku, M., Verstraete, N., Raynal, F., Madrid-Mencía, M., Domagala, M., Fournié, J., Ysebaert, L., Poupot, M., & Pancaldi, V. (2020) · Cancers · doi:10.3390/cancers12123664 · Cited by 16 · see citing works
IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-κB/TGF-β1 pathway
Shinozaki, S., Mashima, H., Ohnishi, H., & Sugano, K. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.01.078 · Cited by 15 · see citing works
Expression of canine interleukin-4 in canine chondrocytes inhibits inflammatory cascade through STAT6
Rachakonda, P. S., Rai, M. F., Manning, K., & Schmidt, M. F. G. (2008) · Cytokine · doi:10.1016/j.cyto.2008.07.470 · Cited by 16 · see citing works
Role of the protease-activated receptor-2 (PAR2) in the exacerbation of house dust mite-induced murine allergic lung disease by multi-walled carbon nanotubes
Lee, H. Y., You, D. J., Taylor-Just, A. J., Tisch, L. J., Bartone, R. D., Atkins, H., Ralph, L. M., Antoniak, S., & Bonner, J. C. (2023) · Particle and Fibre Toxicology · doi:10.1186/s12989-023-00538-6 · Cited by 15 · see citing works
Effect of allergic rhinitis on the expression of human β-defensin 2 in tonsils
Choi, I. J., Rhee, C., Lee, C. H., & Kim, D.-Y. (2013) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2012.12.020 · Cited by 15 · see citing works
Involvement of NF- B in TGF- -mediated suppression of IL-4 signaling
Yamamoto, T., Imoto, S., Sekine, Y., Sugiyama, K., Akimoto, T., Muraguchi, A., & Matsuda, T. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.163 · Cited by 14 · see citing works
MAST CELL-RESTRICTED p70 STAT6 ISOFORM IS A PRODUCT OF SELECTIVE PROTEOLYSIS
Shelburne, C. P., Piekorz, R. P., Bouton, L. A., Chong, H., & Ryan, J. J. (2002) · Cytokine · doi:10.1006/cyto.2002.1957 · Cited by 13 · see citing works
IL-4 Inhibits Expression of the Formyl Peptide Receptor Gene in Mouse Peritoneal Macrophages
Dai, Y., Major, J. A., Novotny, M., & Hamilton, T. A. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.11 · Cited by 13 · see citing works
Genetic control of interleukin-4–induced activation of the human signal transducer and activator of transcription 6 signaling pathway
Zhang, W. J., Koltun, W. A., Tilberg, A. F., Thompson, J. L., & Chorney, M. J. (2003) · Human Immunology · doi:10.1016/s0198-8859(03)00002-8 · Cited by 13 · see citing works
The STAT4 and STAT6 Pathways in Pancreatitis-Associated Lung Injury
Simovic, M. O., Ballard, B. R., Gray, K. D., & Stain, S. C. (2006) · Journal of Surgical Research · doi:10.1016/j.jss.2006.07.032 · Cited by 12 · see citing works
Monoacylglycerol lipase promotes Fcγ receptor-mediated phagocytosis in microglia but does not regulate LPS-induced upregulation of inflammatory cytokines
Kouchi, Z. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.07.019 · Cited by 12 · see citing works
Evaluation of nasal fluid β-defensin 2 levels in children with allergic rhinitis
Dilek, F., Özkaya, E., Gultepe, B. S., Yazıcı, M., Çakır, E., & Gedik, A. H. (2017) · Türk Pediatri Arşivi · doi:10.5152/turkpediatriars.2017.4497 · Cited by 11 · see citing works
Opposing effects of pro‐ and anti‐inflammatory cytokine gene polymorphisms on the risk for breast cancer in western I ndian women: a pilot study
Joshi, N., Bhat, S., Hake, S. S., Kale, M., & Kannan, S. (2013) · International Journal of Immunogenetics · doi:10.1111/iji.12098 · Cited by 10 · see citing works
Meta-analysis of the Correlation Between Interleukin-6 Promoter Polymorphism -174G/C and Interferon Regulatory Factor 4 rs12203592 Polymorphism With Skin Cancer Susceptibility
Wu, M., Cao, Y. L., Liu, Y., Ma, L., & Yang, X. R. (2016) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000000429 · Cited by 10 · see citing works
Dynamic analysis of STAT6 signalling in living cells
Nelson, G., Wilde, G. J. C., Spiller, D. G., Sullivan, E., Unitt, J. F., & White, M. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03672-4 · Cited by 8 · see citing works
Structural-activity relationship of Lycium barbarum polysaccharides in immunomodulation: integrating molecular insights with target identification for therapeutic development
Wang, B., Yang, J., Tao, L., Zhou, X., & Ding, X. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1730418 · Cited by 7 · see citing works
Fire needling acupuncture attenuates synovial inflammation and cartilage degeneration in knee osteoarthritis via SDF-1/CXCR4-mediated macrophage polarization
Wei, J., Yang, X. N., Zhao, L., Liu, X., Ge, X., Zhang, J., Zhou, J., Zhang, C., Song, Y., Li, W., et al. (2025) · Clinical Rheumatology · doi:10.1007/s10067-025-07612-8 · Cited by 6 · see citing works
Leveraging auxiliary data from arbitrary distributions to boost GWAS discovery with Flexible cFDR
Hutchinson, A., Reales, G., Willis, T. W., & Wallace, C. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009853 · Cited by 6 · see citing works
DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets
Bhowmick, D. C., Ahn, M., Bhattacharya, S., Aslamy, A., & Thurmond, D. C. (2024) · Metabolism · doi:10.1016/j.metabol.2025.156132 · Cited by 4 · see citing works
Alternatively activated monocyte-derived myeloid cells promote extracellular pathogen persistence in pulmonary fungal granulomas
Zheng, Y., Pierre, M. J., Ansaldo, E., Dobson, H. E., Kamenyeva, O., Onyishi, C. U., Douglas, S., Febres‐Aldana, C. A., Zerk, P. E., Sereti, I., et al. (2026) · The Journal of Experimental Medicine · doi:10.1084/jem.20260208 · Cited by 3 · see citing works
Modulation of STAT6 signaling for hepatoprotection
Somm, E., Rahman, M., Szántó, I., Gariani, K., & Jornayvaz, F. R. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1659227 · Cited by 2 · see citing works
A high‐fat, high‐sucrose diet exacerbates muscle and metabolic pathology and undermines glucocorticoid efficacy in dystrophin‐deficient mice
Vorwald, M. E., Krishna, S., Lee, J. H., Roths, M. S., Valentine, R. J., & Selsby, J. T. (2026) · The Journal of Physiology · doi:10.1113/jp289832 · Cited by 2 · see citing works
The 2-5A Pathway and Signal Transduction
Verhas, M., Verbinnen, T., Meirleir, K. D., Herst, C. V., Frémont, M., & Englebienne, P. (2002) · CRC Press eBooks · doi:10.1201/9781420041002.ch5 · Cited by 2 · see citing works
The role of modification of innate immunity in development of premature labore
Drukker, N. A., Durnitsyna, O. A., & Александровна, Н. А. (2018) · Biomeditsinskaya Khimiya · doi:10.18097/pbmc20186405439 · Cited by 1 · see citing works
Exploring Asthma as a Protective Factor in COVID-19 Outcomes
Quinn, A. E., Zhao, L., Bell, S. D., Huq, M. H., & Fang, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041678 · Cited by 1 · see citing works
Modulation of innate immune signaling pathways by the intracellular pathogen Toxoplasma gondii
Rosowski, E. E. (2013) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 1 · see citing works
Leveraging auxiliary data from arbitrary distributions to boost GWAS discovery with Flexible cFDRPreprint
Hutchinson, A., Reales, G., Willis, T. W., & Wallace, C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.04.411710 · Cited by 1 · see citing works
MECHANISMS BY WHICH INTERLEUKIN-4 SUPPRESSES INFLAMMATORY CYTOKINE PRODUCTION BY ACTIVATED HUMAN MONOCYTES
Woodward, E. (2011) · Murdoch University Research Portal

STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages
Ohmori, Y., & Hamilton, T. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.29202 · Cited by 102 · see citing works
Interleukin-4 Suppression of Tumor Necrosis Factor α-stimulated E-selectin Gene Transcription Is Mediated by STAT6 Antagonism of NF-κB
Bennett, B. L., Cruz, R., Lacson, R., & Manning, A. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.15.10212 · Cited by 147 · see citing works
Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells
Georas, S. N., Cumberland, J. E., Burke, T. F., Chen, R., Schindler, U., & Casolaro, V. (1998) · Blood · doi:10.1182/blood.v92.12.4529 · Cited by 43 · see citing works
IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages
Ohmori, Y., & Hamilton, T. A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.11.5474 · Cited by 161 · see citing works
Regulation of interleukin 4-mediated signaling by naturally occurring dominant negative and attenuated forms of human Stat6
Patel, B. K. R., Pierce, J. H., & LaRochelle, W. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.172 · Cited by 62 · see citing works

Authors: Ohmori, Y., & Hamilton, T. A.
Affiliations: Cleveland Clinic (US)
Corresponding author: Ohmori, Yoshihiro
ORCID: Ohmori, Yoshihiro
Hamilton, Thomas A.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2000-12
Volume: 275
Issue: 48
Pages: 38095-38103
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m006227200
OpenAlex: W2015491183
Cited by: 106
References: 68
Citations by year: 2026: 3 · 2025: 3 · 2024: 2 · 2023: 4 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 3
FWCI: 3.83
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7244 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA62220, P01CA062220)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: IL-4, STAT6, STAT1, NF-κB, transcriptional repression, interferon-gamma, TNF-α, CREB-binding protein, DNA-binding domain, transcriptional coactivator, inflammatory gene expression
MeSH terms: Base Sequence, Cell Line, DNA-Binding Proteins, Humans, Interferon-gamma, Phosphoproteins, Transcription, Genetic, Tumor Necrosis Factor-alpha, Trans-Activators, Interleukin-4, NF-kappa B, DNA Primers, STAT6 Transcription Factor, Interferon Regulatory Factor-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Interleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks