The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
Open accessAbstract
The hypoxic response is an ancient stress response triggered by low ambient oxygen (O2) (ref. 1) and controlled by hypoxia-inducible transcription factor-1 (HIF-1), whose alpha subunit is rapidly degraded under normoxia but stabilized when O2-dependent prolyl hydroxylases (PHDs) that target its O2-dependent degradation domain are inhibited. Thus, the amount of HIF-1alpha, which controls genes involved in energy metabolism and angiogenesis, is regulated post-translationally. Another ancient stress response is the innate immune response, regulated by several transcription factors, among which NF-kappaB plays a central role. NF-kappaB activation is controlled by IkappaB kinases (IKK), mainly IKK-beta, needed for phosphorylation-induced degradation of IkappaB inhibitors in response to infection and inflammation. IKK-beta is modestly activated in hypoxic cell cultures when PHDs that attenuate its activation are inhibited. However, defining the relationship between NF-kappaB and HIF-1alpha has proven elusive. Using in vitro systems, it was reported that HIF-1alpha activates NF-kappaB, that NF-kappaB controls HIF-1alpha transcription and that HIF-1alpha activation may be concurrent with inhibition of NF-kappaB. Here we show, with the use of mice lacking IKK-beta in different cell types, that NF-kappaB is a critical transcriptional activator of HIF-1alpha and that basal NF-kappaB activity is required for HIF-1alpha protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals. IKK-beta deficiency results in defective induction of HIF-1alpha target genes including vascular endothelial growth factor. IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Additionally, numerous studies have shown that NF-κB regulates the hypoxic response by stimulating the transcription of HIF-1α and HIF-1β, and by inducing IKK-dependent stabilization of HIF-2α [15–17].”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The ERN1 and CAPG genes might also be involved in the innate immune response since hypoxia triggers innate immunity responses through the activation of the hypoxia induced factor α1 (HIF-1α) (Oosthuyse et al., 2001; Rius et al., 2008; Singh et al., 2016).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Rius et al., 2008
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“HIF-1α activation acts in concert with NF-κB activation and boosts antimicrobial immunity (Nizet and Johnson, 2009;Rius et al., 2008).”
From Iron in infection and immunity (2020) · cites this paper as Rius et al., 2008
In the citing paper
“In macrophages, lipopolysaccharide (LPS)-induced HIF1 a accumulation requires nuclear factor (NF)k B- and p42/44 MAPK-dependent transcriptional events (Frede et al., 2006; Rius et al., 2008).”
From Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen (2015) · cites this paper as Rius et al., 2008
In the citing paper
“NF-kB, which is a master regulator of inflammatory responses, is essential for the induction of baseline Hif-1α mRNA [55]”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [55]
In the citing paper
“Recent studies indicate that transcription of HIF-1α is activated by NF-κB-mediated signaling51.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [51]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,976
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Phosphorylation meets ubiquitination: the control of NF-κB activity
Karin, M., & Ben-Neriah, Y. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.621 · Cited by 4,766
Self-citationNuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases
Barnes, P. J., & Karin, M. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704103361506 · Cited by 4,622
Self-citationCellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068
HIF-1α is essential for myeloid cell-mediated inflammation
Cramer, T., Yamanishi, Y., Clausen, B. E., Förster, I., Pawlinski, R., Mackman, N., Haase, V. H., Jaenisch, R., Corr, M., Nizet, V., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00154-5 · Cited by 2,046
Self-citationHIF‐1α is required for solid tumor formation and embryonic vascularization
Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579
Self-citationGeneral involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4304 · Cited by 1,468
Regulation and Function of IKK and IKK-Related Kinases
Häcker, H., & Karin, M. (2006) · Science s STKE · doi:10.1126/stke.3572006re13 · Cited by 1,298
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 1,001
TOLL-LIKE RECEPTORS IN ISCHEMIA-REPERFUSION INJURY
Arumugam, T. V., Okun, E., Tang, S., Thundyil, J., Taylor, S. M., & Woodruff, T. M. (2009) · Shock · doi:10.1097/shk.0b013e318193e333 · Cited by 308
Metabolic Modulation in Macrophage Effector Function
Diskin, C., & Pålsson‐McDermott, E. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00270 · Cited by 310
Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases
Nath, B., & Szabó, G. (2011) · Hepatology · doi:10.1002/hep.25497 · Cited by 295
The roles of cathelicidin LL-37 in immune defences and novel clinical applications
Nijnik, A., & Hancock, R. E. W. (2008) · Current Opinion in Hematology · doi:10.1097/moh.0b013e32831ac517 · Cited by 290
Macrophages, Inflammation, and Lung Cancer
Conway, E. M., Pikor, L. A., Kung, S. H. Y., Hamilton, M. J., Lam, S. C., Lam, W. L., & Bennewith, K. L. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201508-1545ci · Cited by 295
Mucus hypersecretion in asthma: causes and effects
Evans, C. M., Kim, K., Tuvim, M. J., & Dickey, B. F. (2008) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e32831da8d3 · Cited by 289
Anti‐tumour strategies aiming to target tumour‐associated macrophages
Tang, X., Mo, C., Wang, Y., Wei, D., & Xiao, H. (2012) · Immunology · doi:10.1111/imm.12023 · Cited by 288
Hypoxia and Hypoxia-Inducible Factors in Kidney Injury and Repair
Shu, S., Wang, Y. X., Zheng, M., Liu, Z., Cai, J., Tang, C., & Dong, Z. (2019) · Cells · doi:10.3390/cells8030207 · Cited by 273
Microenvironment and tumor cell plasticity: An easy way out
Taddei, M. L., Giannoni, E., Comito, G., & Chiarugi, P. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.01.042 · Cited by 272
Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications
Silvestre, J., Smadja, D. M., & Levy, B. I. (2013) · Physiological Reviews · doi:10.1152/physrev.00006.2013 · Cited by 281
Hasselbalch, H. C. (2012) · Leukemia Research · doi:10.1016/j.leukres.2012.10.020 · Cited by 261
Differentiation and gene expression profile of tumor-associated macrophages
Schmieder, A., Michel, J., Schönhaar, K., Goerdt, S., & Schledzewski, K. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.02.002 · Cited by 263
Metabolic regulation of macrophage phenotype and function
Saha, S., Shalova, I. N., & Biswas, S. K. (2017) · Immunological Reviews · doi:10.1111/imr.12603 · Cited by 260
NF-κB pathways in the development and progression of colorectal cancer
Patel, M., Horgan, P. G., McMillan, D. C., & Edwards, J. (2018) · Translational research · doi:10.1016/j.trsl.2018.02.002 · Cited by 254
Cellular and molecular pathways linking inflammation and cancer
Porta, C., Larghi, P., Rimoldi, M., Totaro, M. G., Allavena, P., Mantovani, A., & Sica, A. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.06.014 · Cited by 262
Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea
McNicholas, W. T. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200903-0347pp · Cited by 249
Adenosine: An Old Drug Newly Discovered
Eltzschig, H. K., Warner, D. S., & Warner, M. A. A. (2009) · Anesthesiology · doi:10.1097/aln.0b013e3181b060f2 · Cited by 253
Regulation of macrophage function in tumors: the multifaceted role of NF-κB
Hagemann, T., Biswas, S. K., Lawrence, T., Sica, A., & Lewis, C. E. (2009) · Blood · doi:10.1182/blood-2008-12-172825 · Cited by 249
He, Q., Gao, Z., Yin, J., Zhang, J., Yun, Z., & Ye, J. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00626.2010 · Cited by 260
Qiu, G., Jin, M., Dai, J., Sun, W., Feng, J., & Jin, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.05.002 · Cited by 250
Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses
Choi, I., Son, H., & Baek, J.-H. (2021) · Life · doi:10.3390/life11010069 · Cited by 262
Bhat, A. A., Nisar, S., Singh, M. K., Ashraf, B., Masoodi, T., Prasad, C. P., Sharma, A., Maacha, S., Karedath, T., Hashem, S., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12295 · Cited by 251
A Polymorphism in npr-1 Is a Behavioral Determinant of Pathogen Susceptibility in C. elegans
Reddy, K. C., Andersen, E. C., Kruglyak, L., & Kim, D. H. (2009) · Science · doi:10.1126/science.1166527 · Cited by 244
Yang, W., Xia, Y., Cao, Y. J., Zheng, Y., Bu, W., Zhang, L., You, M. J., Koh, M. Y., Cote, G. J., Aldape, K., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.028 · Cited by 250
Tumor-associated macrophages: role in cancer development and therapeutic implications
Salmaninejad, A., Valilou, S. F., Soltani, A., Ahmadi, S., Abarghan, Y. J., Rosengren, R. J., & Sahebkar, A. (2019) · Cellular Oncology · doi:10.1007/s13402-019-00453-z · Cited by 251
Fujisaka, S., Usui, I., Ikutani, M., Aminuddin, A., Takikawa, A., Tsuneyama, K., Mahmood, A., Goda, N., Nagai, Y., Takatsu, K., et al. (2013) · Diabetologia · doi:10.1007/s00125-013-2885-1 · Cited by 239
The Roles of Hypoxia Signaling in the Pathogenesis of Cardiovascular Diseases
Abe, H., Semba, H., & Takeda, N. (2017) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.rv17009 · Cited by 244
Zhang, Y., Fei, M., Xue, G., Zhou, Q., Jia, Y., Li, L., Xin, H., & Sun, S. (2012) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01291.x · Cited by 236
Inflammation and Hypoxia: HIF and PHD Isoform Selectivity
Watts, E., & Walmsley, S. R. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.10.006 · Cited by 248
Zhang, J., Malik, A., Choi, H. B., Ko, R. W. Y., Dissing-Olesen, L., & MacVicar, B. A. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.043 · Cited by 234
McNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234
Platelet-to-lymphocyte ratio in advanced Cancer: Review and meta-analysis
Li, B., Zhou, P., Liu, Y., Wei, H., Yang, X., Chen, T., & Xiao, J. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.04.023 · Cited by 234
Metabolic transformation in cancer
Tennant, D. A., Durán, R. V., Boulahbel, H., & Gottlieb, E. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp070 · Cited by 235
Regulatory mechanisms of hypoxia‐inducible factor 1 activity: Two decades of knowledge
Koyasu, S., Kobayashi, M., Gotö, Y., Hiraoka, M., & Harada, H. (2017) · Cancer Science · doi:10.1111/cas.13483 · Cited by 233
Brahimi-Horn, M. C., & Pouysségur, J. (2009) · Journal of Cell Science · doi:10.1242/jcs.035022 · Cited by 236
The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis
Carmi, Y., Voronov, E., Dotan, S., Lahat, N., Rahat, M. A., Fogel, M., Huszar, M., White, M. R., Dinarello, C. A., & Apte, R. N. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901511 · Cited by 224
Li, Z., Lv, L., Tang, T., Wang, B., Ye, F., Zhou, L., Cao, J.-Y., Tang, R., Wu, M., Liu, H., et al. (2018) · Kidney International · doi:10.1016/j.kint.2018.09.013 · Cited by 223
Signalling pathways involved in hypoxia‐induced renal fibrosis
Liu, M., Ning, X., Li, R., Yang, Z. L., Yang, X., Sun, S., & Qian, Q. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13060 · Cited by 223
Hypoxia and extracellular vesicles: A review on methods, vesicular cargo and functions
Korvenlaita, N., Pistono, C., Huremagic, B., Jolkkonen, J., Giugno, R., & Malm, T. (2020) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12002 · Cited by 221
Hypoxia and inflammation are two sides of the same coin
Bartels, K., Grenz, A., & Eltzschig, H. K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318345110 · Cited by 218
Hypoxia-dependent regulation of inflammatory pathways in immune cells
Taylor, C. T., Doherty, G. A., Fallon, P. G., & Cummins, E. P. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84433 · Cited by 224
Pugliese, S. C., Poth, J. M., Fini, M. A., Olschewski, A., Kasmi, K. C. E., & Stenmark, K. R. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00238.2014 · Cited by 218
Molecular Pathogenesis of NASH
Caligiuri, A., Gentilini, A., & Marra, F. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091575 · Cited by 219
Feng, S., Bowden, N., Fragiadaki, M., Souilhol, C., Hsiao, S. T.-F., Mahmoud, M. M., Allen, S. P., Pirri, D., Ayllón, B. T., Akhtar, S., et al. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309249 · Cited by 215
Yang, S., Tang, Z., Hu, C., Zhang, D., Shen, N., Yu, H., & Chen, X. (2019) · Advanced Materials · doi:10.1002/adma.201805955 · Cited by 210
Iannetti, A., Pacifico, F., Acquaviva, R., Lavorgna, A., Crescenzi, E., Vascotto, C., Tell, G., Salzano, A. M., Scaloni, A., Vuttariello, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710846105 · Cited by 210
Li, K., Xu, W., Guo, Q., Jiang, Z., Wang, P., Yue, Y., & Xiong, S. (2009) · Circulation Research · doi:10.1161/circresaha.109.195230 · Cited by 211
Lechner, M. G., Megiel, C., Russell, S. M., Bingham, B., Arger, N., Woo, T. T., & Epstein, A. L. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-90 · Cited by 208
Caveolae and signalling in cancer
Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. P. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3915 · Cited by 216
HIF-1 in the inflammatory microenvironment
Dehne, N., & Brüne, B. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.03.019 · Cited by 211
Lee, J. H., Elly, C., Park, Y., & Liu, Y. (2015) · Immunity · doi:10.1016/j.immuni.2015.05.016 · Cited by 211
The Role of Tumor Inflammatory Microenvironment in Lung Cancer
Tan, Z., Xue, H., Sun, Y., Zhang, C., Song, Y., & Qi, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.688625 · Cited by 210
Liu, G., Bi, Y., Shen, B., Yang, H., Zhang, Y., Wang, X., Liu, H., Lu, Y., Liao, J., Chen, X., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-2584 · Cited by 205
Transduction of Redox Signaling by Electrophile-Protein Reactions
Rudolph, T. K., & Freeman, B. Α. (2009) · Science Signaling · doi:10.1126/scisignal.290re7 · Cited by 203
Hypoxia-inducible factors: a central link between inflammation and cancer
Triner, D., & Shah, Y. M. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84430 · Cited by 199
Li, F., Zhang, J., Arfuso, F., Chinnathambi, A., Zayed, M. E., Alharbi, S. A., Kumar, A. P., Ahn, K. S., & Sethi, G. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1470-4 · Cited by 199
More than an anticoagulant: Do heparins have direct anti-inflammatory effects?
Poterucha, T. J., Libby, P., & Goldhaber, S. Z. (2016) · Thrombosis and Haemostasis · doi:10.1160/th16-08-0620 · Cited by 198
Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis
Saxena, K., Jolly, M. K., & Balamurugan, K. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.100845 · Cited by 205
Croci, D. O., Salatino, M., Rubinstein, N., Cerliani, J. P., Cavallin, L. E., Leung, H. J., Ouyang, J., Ilarregui, J. M., Toscano, M. A., Domaica, C. I., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111665 · Cited by 197
Roles of NF-κB in health and disease: mechanisms and therapeutic potential
Wong, E. T., & Tergaonkar, V. (2009) · Clinical Science · doi:10.1042/cs20080502 · Cited by 196
Nitric Oxide, Cytochrome C Oxidase, and the Cellular Response to Hypoxia
Taylor, C. T., & Moncada, S. (2010) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.181628 · Cited by 220
The hypoxia signaling pathway and hypoxic adaptation in fishes
Xiao, W. (2015) · Science China Life Sciences · doi:10.1007/s11427-015-4801-z · Cited by 195
NF-κB Regulation: The Nuclear Response
Mankan, A. K., Lawless, M. W., Gray, S. G., Kelleher, D. P., & McManus, R. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00632.x · Cited by 193
Szebeni, G. J., Vízler, C., Kitajka, K., & Puskás, L. G. (2017) · Mediators of Inflammation · doi:10.1155/2017/9294018 · Cited by 195
Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway
Sondermann, N. C., Faßbender, S., Hartung, F., Hätälä, A. M., Rolfes, K. M., Vogel, C. F. A., & Haarmann‐Stemmann, T. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115371 · Cited by 205
Storci, G., Sansone, P., Mari, S., D’Uva, G., Tavolari, S., Guarnieri, T., Taffurelli, M., Ceccarelli, C., Santini, D., Chieco, P., et al. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22264 · Cited by 188
Immune cell subset differentiation and tissue inflammation
Fang, P., Li, X., Dai, J., Cole, L. E., Camacho, J. A., Zhang, Y., Ji, Y. H., Wang, J., Yang, X., & Wang, H. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0637-x · Cited by 189
Targeting microRNAs as key modulators of tumor immune response
Paladini, L., Fabris, L., Bottai, G., Raschioni, C., Călin, G. A., & Santarpia, L. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0375-2 · Cited by 184
(2009) · PubMed · Cited by 183
Hsieh, T.-P., Sheu, S.-Y., Sun, J., & Chen, M. (2010) · Phytomedicine · doi:10.1016/j.phymed.2010.04.003 · Cited by 184
IL-21 and T follicular helper cells
Spolski, R. J., & Leonard, W. J. (2009) · International Immunology · doi:10.1093/intimm/dxp112 · Cited by 192
Hypoxia and HIF Signaling: One Axis with Divergent Effects
Corrado, C., & Fontana, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165611 · Cited by 184
Hypoxia-inducible factors and innate immunity in liver cancer
Yuen, V. W., & Wong, C. C. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137553 · Cited by 187
Molecular pathways and targets in cancer-related inflammation
Mantovani, A., Garlanda, C., & Allavena, P. (2010) · Annals of Medicine · doi:10.3109/07853890903405753 · Cited by 182
Bao, B., Azmi, A. S., Ali, S. S., Ahmad, A., Li, Y., Banerjee, S., Kong, D., & Sarkar, F. H. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.04.008 · Cited by 181
Hypoxia-induced epithelial to mesenchymal transition in cancer
Hapke, R., & Haake, S. M. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.05.012 · Cited by 184
The role of hypoxia in inflammatory disease (Review)
Biddlestone, J., Bandarra, D., & Rocha, S. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2079 · Cited by 183
The mechanism of Warburg effect-induced chemoresistance in cancer
Liu, C., Jin, Y., & Fan, Z. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.698023 · Cited by 177
Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells
O’Rourke, R. W., White, A. E., Metcalf, M. D., Olivas, A., Mitra, P., Larison, W. G., Cheang, E. C., Varlamov, O., Corless, C. L., Roberts, C. T., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2103-y · Cited by 177
Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism
Burgos, R. A., Alarcón, P., Quiroga, J., Manosalva, C., & Hancke, J. L. (2020) · Molecules · doi:10.3390/molecules26010005 · Cited by 177
The Role of NF‐κB in Hypoxia‐Induced Gene Expression
Taylor, C. T., & Cummins, E. P. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05024.x · Cited by 175
Hypoxia-Inducible Factor Signaling in Pheochromocytoma: Turning the Rudder in the Right Direction
Jochmanová, I., Yang, C., Zhuang, Z., & Pacák, K. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt201 · Cited by 176
Hypoxia and tissue destruction in pulmonary TB
Belton, M., Brilha, S., Manavaki, R., Mauri, F. A., Nijran, K. S., Hong, Y. T., Patel, N., Dembek, M., Tezera, L. B., Green, J. A., et al. (2016) · Thorax · doi:10.1136/thoraxjnl-2015-207402 · Cited by 174
Hill, D. R., Huang, S., Nagy, M. S., Yadagiri, V. K., Fields, C., Thornhill, D., Bons, B., Dedhia, P. H., Chin, A. M., Tsai, Y.-H., et al. (2017) · eLife · doi:10.7554/elife.29132 · Cited by 179
Bolignano, D., Donato, V., Lacquaniti, A., Fazio, M. R., Bono, C., Coppolino, G., & Buemi, M. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.05.027 · Cited by 172
Tafani, M., Schito, L., Pellegrini, L., Villanova, L., Marfè, G., Anwar, T., Rosa, R., Indelicato, M., Fini, M., Pucci, B., et al. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr101 · Cited by 172
Hypoxia-inducible factors: key regulators of myeloid cells during inflammation
Lin, N., & Simon, M. C. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84426 · Cited by 170
Functional regulation of HIF‐1α under normoxia—is there more than post‐translational regulation?
Kuschel, A., Simon, P. D., & Tug, S. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22798 · Cited by 174
Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment
Zhang, H., Li, S., Wang, D., Liu, S. M., Xiao, T., Gu, W., Yang, H., Wang, H. Z., Yang, M., & Chen, P. (2024) · Biomarker Research · doi:10.1186/s40364-024-00646-1 · Cited by 178
Marrocco, A., & Ortiz, L. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.936167 · Cited by 173
Macrophages in vascular inflammation and atherosclerosis
Cochain, C., & Zernecke, A. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1941-y · Cited by 168
Evolutionary Conserved Regulation of HIF-1β by NF-κB
van Uden, P., Kenneth, N. S., Webster, R., Müller, H. A., Mudie, S., & Rocha, S. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001285 · Cited by 163
Inflammation, DNA methylation and colitis-associated cancer
Hartnett, L., & Egan, L. J. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs006 · Cited by 165
The pleiotropic effects of erythropoietin in infection and inflammation
Nairz, M., Sonnweber, T., Schroll, A., Theurl, I., & Weiss, G. (2012) · Microbes and Infection · doi:10.1016/j.micinf.2011.10.005 · Cited by 161
Saggu, R., Schumacher, T., Gerich, F. J., Rakers, C., Tai, K., Delekate, A., & Petzold, G. C. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0350-3 · Cited by 160
NF-κB as a central regulator of macrophage function in tumors
Biswas, S. K., & Lewis, C. E. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0310153 · Cited by 166
Olson, N. C., & van der Vliet, A. (2011) · Nitric Oxide · doi:10.1016/j.niox.2010.12.010 · Cited by 161
Li, Y., Jia, H., Yu, W., Xu, Y., Li, X., Li, Q., & Cai, S. (2016) · International Journal of Cancer · doi:10.1002/ijc.30071 · Cited by 162
Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis
Pamenter, M. E., & Powell, F. L. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150026 · Cited by 169
Qing, G., Skuli, N., Mayes, P. A., Pawel, B., Martinez, D., Maris, J. M., & Simon, M. C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0740 · Cited by 157
Metadata
- Authors
- Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., & Karin, M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Karin, Michael
- ORCID
- Venue
- Nature
- Published
- 2008-04-23
- Volume
- 453
- Issue
- 7196
- Pages
- 807-811
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2669289
- OpenAlex
- W2162121911
- Cited by
- 1,614
- References
- 34
- Citations by year
- 2026: 89 · 2025: 85 · 2024: 79 · 2023: 78 · 2022: 81 · 2021: 107 · 2020: 79 · 2019: 77 · 2018: 82 · 2017: 70 · 2016: 97 · 2015: 95 · 2014: 105 · 2013: 91 · 2012: 89
- FWCI
- 35.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA118165)
- National Institute of Allergy and Infectious Diseases (R01AI043477)
- National Center for Research Resources (P41RR004050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- NF-κB, HIF-1α, hypoxia response, innate immunity, IKKβ, transcriptional regulation, prolyl hydroxylase, oxygen-dependent degradation, inflammation, liver, brain, hypoxia-inducible factor, IκB kinase, oxygen sensing
- MeSH terms
- Animals, Hypoxia, Brain, Gene Expression Regulation, Immunity, Innate, Inflammation, Liver, Macrophages, Transcription, Genetic, Cell Hypoxia, NF-kappa B, Mice, I-kappa B Kinase, Hypoxia-Inducible Factor 1, alpha Subunit
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
