Cited by 647Inflammatory mediators and NSAID effectsNF-κB Signaling PathwaysSignaling Pathways in Disease

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Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells.

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Yamamoto, Kei, Arakawa, Toshiya, Ueda, Natsuo, Yamamoto, Shozo·1995·Journal of Biological Chemistry

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Abstract

When a mouse osteoblastic cell line MC3T3-E1 was cultured in the presence of tumor necrosis factor alpha (TNF alpha), the release of prostaglandin E2 and the cyclooxygenase activity increased in a dose- and time-dependent manner. The increase of the enzyme activity was attributed mostly to the induction of cyclooxygenase-2 rather than cyclooxygenase-1 as judged by the inhibitory effect of NS398, Western blotting, and Northern blotting. In this system we attempted to elucidate the transcriptional regulation of the cyclooxygenase-2 gene. As examined by the luciferase assay, two positive regulatory regions (-186 to -131 and -512 to -385 base pairs) were found in the 5'-flanking promoter region of the mouse cyclooxygenase-2 gene in the TNF alpha-stimulated cells. The former included putative NF-IL6 (C/EBP beta) and AP2 elements, and the latter contained the NF kappa B motif. A DNA probe including the NF-IL6 and AP2 sites gave positive bands upon electrophoretic mobility shift assay using the nuclear extracts of MC3T3-E1 cells. The bands were supershifted by the addition of anti-NF-IL6 antibody but not by anti-AP2 antibody. A probe including the NF kappa B site also gave positive bands, which were supershifted by anti-NF kappa B p50 and p65 antibodies. Furthermore, when the motif of NF-IL6 or NF kappa B or both was subjected to point mutation, the luciferase activity was markedly reduced. These data suggested a potential role of both NF-IL6 and NF kappa B in the induction of cyclooxygenase-2 by TNF alpha.

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Helicobacter pylori-induced Expression of Interleukin-8 and Cyclooxygenase-2 in AGS Gastric Epithelial Cells: Mediation by Nuclear Factor-?B
Kim, H., Lim, J. W., & Kim, K. H. (2001) · Scandinavian Journal of Gastroenterology · doi:10.1080/003655201300191969 · Cited by 73
Coronarin D, a labdane diterpene, inhibits both constitutive and inducible nuclear factor-κB pathway activation, leading to potentiation of apoptosis, inhibition of invasion, and suppression of osteoclastogenesis
Kunnumakkara, A. B., Ichikawa, H., Anand, P., Mohankumar, C. J., Hema, P. S., Nair, M. S., & Aggarwal, B. B. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0432 · Cited by 73
Retracted
Cyclosporine A Suppresses Cyclooxygenase-2 Expression in the Rat Kidney
Höcherl, K., Dreher, F., Vitzthum, H., Diaeresis]hler, J. K., & Kurtz, A. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000031702.86799.b9 · Cited by 71
Activation of peroxisome proliferator–activated receptor-γ inhibits differentiation of preosteoblasts
Khan, E., & Abu‐Amer, Y. (2003) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(03)00058-1 · Cited by 70
Tumor necrosis factor-$alpha; does not modulate ischemia/reperfusion injury in na�ve myocardium but is essential for the development of late preconditioning*1
DAWN, B. (2004) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2004.03.012 · Cited by 69
“Similarly, the induction of COX-2, a comediator of late PC [7], is regulated by the activation of the jB-binding site in its promoter region [50].”
Background
Polymethoxy Flavonoids, Nobiletin and Tangeretin, Prevent Lipopolysaccharide-Induced Inflammatory Bone Loss in an Experimental Model for Periodontitis
Tominari, T., Hirata, M., Matsumoto, C., Inada, M., & Miyaura, C. (2012) · Journal of Pharmacological Sciences · doi:10.1254/jphs.11188sc · Cited by 69
Anti-inflammatory effect of coumarins isolated from Corydalis heterocarpa in HT-29 human colon carcinoma cells
Kang, K., Kong, C., Seo, Y., Kim, M., & Kim, S. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.05.036 · Cited by 69
Ergolide, sesquiterpene lactone from Inula britannica, inhibits inducible nitric oxide synthase and cyclo‐oxygenase‐2 expression in RAW 264.7 macrophages through the inactivation of NF‐κB
Han, J. W., Lee, B. G., Kim, Y. K., Yoon, J., Jin, H. K., Hong, S., Lee, H. Y., Lee, K. R., & Lee, H. W. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704099 · Cited by 69
“There are indications that activation of NF-kB is involved in iNOS and COX-2 expression because there is an NF-kB consensus site in the upstream promotor region of the iNOS and COX-2 gene (Yamamoto et al., 1995; Kim et al., 1997; Barnes & Karin, 1997; Cro ord et al., 1997).”
Background
Cyclooxygenase 1 and cyclooxygenase 2 expression is abnormally regulated in human nasal polyps
Mullol, J., Fernández-Morata, J., Roca‐Ferrer, J., Pujols, L., Xaubet, A., Benitez, P. A., & Picado, C. (2002) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2002.123534 · Cited by 69
Posttranscriptional Regulation of Cyclooxygenase-2 in Rat Intestinal Epithelial Cells
Zhang, Z., Sheng, H., Shao, J., Beauchamp, R. D., & DuBois, R. N. (2000) · Neoplasia · doi:10.1038/sj.neo.7900117 · Cited by 69
Regulation of Cyclooxygenase-2 Expression by Nitric Oxide in Cells
Pérez‐Sala, D., & Lamas, S. (2001) · Antioxidants and Redox Signaling · doi:10.1089/152308601300185197 · Cited by 70
“The up-stream site is involved in IL-1 b - and TNF-a - elicited COX-2 induction (86, 137).”
Activation of NFκB is necessary for IL-1β-induced cyclooxygenase-2 (COX-2) expression in human gingival fibroblasts
Nakao, S., Ogata, Y., Shimizu-Sasaki, E., Yamazaki, M., Furuyama, S., & Sugiya, H. (2000) · Molecular and Cellular Biochemistry · doi:10.1023/a:1007155525020 · Cited by 69
Novel Regulation of Cyclooxygenase-2 Expression and Prostaglandin E2 Production by IFN-γ in Human Macrophages
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β-Caryophyllene oxide potentiates TNFα-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products
Kim, C., Cho, S. K., Kim, K.-D., Nam, D., Chung, W., Jang, H.-J., Lee, S., Shim, B. S., Sethi, G., & Ahn, K. S. (2013) · APOPTOSIS · doi:10.1007/s10495-013-0957-9 · Cited by 73
Macrolide Therapy in Chronic Inflammatory Diseases
Kwiatkowska, B., & Maślińska, M. (2012) · Mediators of Inflammation · doi:10.1155/2012/636157 · Cited by 68
“Expression of genes involved in immune response and inflammation (e.g., iNOS, COX-2, TNF-alpha, IL-1, and IL-6) at the level of transcription is regulated by nuclear factor-kappa B (NF-κB) [13].”
Background
Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease
Ciesielska, A., Joniec‐Maciejak, I., Przybyłkowski, A. M., Gromadzka, G., Iwona, Członkowska, A., & Członkowski, A. (2003) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2003-1461 · Cited by 68
Suppression of cyclooxygenase‐2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid
Yamamoto, K., Wang, J., Yamamoto, S., & Tobe, H. (2000) · FEBS Letters · doi:10.1016/s0014-5793(99)01727-5 · Cited by 68
Signaling Mechanisms Involved in the Activation of Arachidonic Acid Metabolism in Human Astrocytoma Cells by Tumor Necrosis Factor‐α
Hernández, M., Bayón, Y., Crespo, M. S., & Nieto, M. L. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0731641.x · Cited by 68
“Moreover, TNF-a is a potent activator of the transcription factor NF-kB, and there are twokB-binding sites in the human COX-2 promoter, the functional relevance of which has been shown in different studies (Coyne et al., 1992; Jones et al., 1993; Yamamoto et al., 1995).”
Background
The role of cyclooxygenase-2 (COX-2) in breast cancer, and implications of COX-2 inhibition
Singh‐Ranger, G., & Mokbel, K. (2002) · European Journal of Surgical Oncology · doi:10.1053/ejso.2002.1329 · Cited by 68
Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation
Ellrichmann, G., Thöne, J., Lee, D.-H., Rupec, R., Gold, R., & Linker, R. A. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-15 · Cited by 70
“via the inducible nitric oxide synthase (iNOS) [10] or cyclooxygenase-2 (COX-2) [11].”
Background
Correlation of prostaglandin E2 concentrations in synovial fluid with ground reaction forces and clinical variables for pain or inflammation in dogs with osteoarthritis induced by transection of the cranial cruciate ligament
Trumble, T. N., Billinghurst, R. C., & McIlwraith, C. W. (2004) · American Journal of Veterinary Research · doi:10.2460/ajvr.2004.65.1269 · Cited by 67
Thiocolchicoside Exhibits Anticancer Effects through Downregulation of NF-κB Pathway and Its Regulated Gene Products Linked to Inflammation and Cancer
Reuter, S., Prasad, S., Phromnoi, K., Ravindran, J., Sung, B., Yadav, V. R., Kannappan, R., Chaturvedi, M. M., & Aggarwal, B. B. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0037 · Cited by 67
Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice
Turnbull, A. V., Prehar, S., Kennedy, A. R., Little, R. A., & Hopkins, S. J. (2003) · Endocrinology · doi:10.1210/en.2002-220964 · Cited by 66
“One of the conundrums is that IL-6 is remarkably noninflammatory in tissues, and although there are some reports that IL-6 induces PGs in non-CNS cells, this seems to be uncommon and to occur at quite high concentrations (57) despite the presence of a nuclear factor IL-6 site upstream of the COX-2 gene (58).”
Background
ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
Santarsiero, A., Convertini, P., Todisco, S., Pierri, C. L., Grassi, A., Williams, N. C., Iacobazzi, D., Stefano, G. D., O'Neill, L. A. J., & Infantino, V. (2021) · Cells · doi:10.3390/cells10112962 · Cited by 68
Relation Between Interleukin-18 and PGE2 in Synovial Fluid of Osteoarthritis: A Potential Therapeutic Target of Cartilage Degradation
Futani, H., Okayama, A., Matsui, K., Kashiwamura, S., Sasaki, T., Hada, T., Nakanishi, K., 立石, 博., Maruo, S., & Okamura, H. (2002) · Journal of Immunotherapy · doi:10.1097/00002371-200203001-00009 · Cited by 66
“stimulation of PGE2 production through upregulation of cyclooxygenase (COX)-2 (5,14,15).”
Background
Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma
Neelgundmath, M., Dinesh, K. R., Mohan, C. D., Li, F., Dai, X., Siveen, K. S., Paricharak, S., Mason, D. J., Fuchs, J. E., Sethi, G., et al. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.12.065 · Cited by 65
Multipotential and systemic effects of traumatic brain injury
Sabet, N., Soltani, Z., & Khaksari, M. (2021) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2021.577619 · Cited by 70
Cyclooxygenase-2 in Myocardium Stimulation by Angiotensin-II in Cultured Cardiac Fibroblasts and Role at Acute Myocardial Infarction
Scheuren, N., Jacobs, M., Ertl, G., & Schorb, W. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2001.1484 · Cited by 65
Nuclear factor κB is activated in small intestinal mucosa of celiac patients
Maiuri, M. C., Stefano, D. D., Mele, G., Fecarotta, S., Greco, L., Troncone, R., & Carnuccio, R. (2003) · Journal of Molecular Medicine · doi:10.1007/s00109-003-0440-0 · Cited by 65
Promoter hypermethylation silences cyclooxygenase-2 (Cox-2) and regulates growth of human hepatocellular carcinoma cells
Murata, H., Tsuji, S., Tsujii, M., Sakaguchi, Y., Fu, H. Y., Kawano, S., & Hori, M. (2004) · Laboratory Investigation · doi:10.1038/labinvest.3700118 · Cited by 64
Additive effect of combined pollutants to UV induced skin OxInflammation damage. Evaluating the protective topical application of a cosmeceutical mixture formulation
Ferrara, F., Woodby, B. L., Pecorelli, A., Schiavone, M. L., Pambianchi, E., Messano, N., Therrien, J., Choudhary, H., & Valacchi, G. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101481 · Cited by 64
RETRACTED ARTICLE: Local administration of transcription factor decoy oligonucleotides to nuclear factor-κB prevents carrageenin-induced inflammation in rat hind paw
D’Acquisto, F., Ialenti, A., Ianaro, A., Vaio, R. D., & Carnuccio, R. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301295 · Cited by 65
Retracted
Dual Effect of Nitric Oxide Donors on Cyclooxygenase-2 Expression in Human Mesangial Cells
Dı́az-Cazorla, M., Pérez‐Sala, D., & Lamas, S. (1999) · Journal of the American Society of Nephrology · doi:10.1681/asn.v105943 · Cited by 64
Tilmicosin and tylosin have anti-inflammatory properties via modulation of COX-2 and iNOS gene expression and production of cytokines in LPS-induced macrophages and monocytes
Cao, X., DONG, M., Shen, J., WU, B., Wu, C., Du, X., Wang, Z., QI, Y., & Лі, Б. (2006) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2005.12.010 · Cited by 63
Up-regulation of Cyclooxygenase-2 Expression and Prostaglandin Synthesis in Endometrial Stromal Cells by Malignant Endometrial Epithelial Cells
Tamura, M., Sebastian, S., Yang, S., Gürateş, B., Ferrer, K., Sasano, H., Okamura, K., & Bulun, S. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201347200 · Cited by 63
Involvement of reactive oxygen species in cyclic stretch‐induced NF‐κB activation in human fibroblast cells
Amma, H., Naruse, K., Ishiguro, N., & Sokabe, M. (2005) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706182 · Cited by 62
“…stimuli, hormones and mitogens, such as transforming growth factor b (TGF-b) (Sumitani et al., 1989; Jackson et al., 1993; Roy et al., 1996), interleukin-1 (IL-1) (Hla & Neilson, 1992; Jackson et al., 1993; Roy et al., 1996), and tumor necrosis factor a (TNF-a) (Yamamoto et al., 1995).”
Background
IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2
Li, Y., Shi, J., Qi, S., Zhang, J., Peng, D., Chen, Z., Wang, G., Wang, Z., & Wang, L. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0839-7 · Cited by 62

Authors: Yamamoto, K., Arakawa, T., Ueda, N., & Yamamoto, S.
Affiliations: Tokushima University (JP)
Corresponding author: Yamamoto, Kei
Yamamoto, Shozo
ORCID: Yamamoto, Kei
Arakawa, Toshiya
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1995-12
Volume: 270
Issue: 52
Pages: 31315-31320
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.270.52.31315
OpenAlex: W2002708977
Cited by: 647
References: 38
Citations by year: 2026: 2 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 3 · 2021: 17 · 2020: 8 · 2019: 11 · 2018: 12 · 2017: 8 · 2016: 10 · 2015: 8 · 2014: 10 · 2013: 15 · 2012: 14
FWCI: 17.65
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, 9116 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Japan Foundation for Applied Enzymology
Japan Research Foundation for Clinical Pharmacology
Kissei
Ono Pharmaceutical
Japan Society for the Promotion of Science
Daiichi Sankyo Company
Topics: Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: cyclooxygenase-2, NF-κB, NF-IL6, C/EBPβ, TNF-α, transcriptional regulation, prostaglandin E2, MC3T3-E1 cells, osteoblasts, promoter regulation, gene induction
MeSH terms: Animals, Base Sequence, DNA-Binding Proteins, Enzyme Induction, Isoenzymes, Molecular Sequence Data, Nuclear Proteins, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Tumor Necrosis Factor-alpha, NF-kappa B, 3T3 Cells, CCAAT-Enhancer-Binding Proteins, Mice

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Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells.

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