NF-κB Is a Negative Regulator of IL-1β Secretion as Revealed by Genetic and Pharmacological Inhibition of IKKβ
Open accessAbstract
IKKbeta-dependent NF-kappaB activation plays a key role in innate immunity and inflammation, and inhibition of IKKbeta has been considered as a likely anti-inflammatory therapy. Surprisingly, however, mice with a targeted IKKbeta deletion in myeloid cells are more susceptible to endotoxin-induced shock than control mice. Increased endotoxin susceptibility is associated with elevated plasma IL-1beta as a result of increased pro-IL-1beta processing, which was also seen upon bacterial infection. In macrophages enhanced pro-IL-1beta processing depends on caspase-1, whose activation is inhibited by NF-kappaB-dependent gene products. In neutrophils, however, IL-1beta secretion is caspase-1 independent and depends on serine proteases, whose activity is also inhibited by NF-kappaB gene products. Prolonged pharmacologic inhibition of IKKbeta also augments IL-1beta secretion upon endotoxin challenge. These results unravel an unanticipated role for IKKbeta-dependent NF-kappaB signaling in the negative control of IL-1beta production and highlight potential complications of long-term IKKbeta inhibition.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Multiple components of molecular machinery for necroptosis-including ZBP1, RIPK3, MLKL, and TNFR1 (mainly via NF-κB)-impinge on control of inflammasome, a supramolecular platform for activation of CASP1 and consequent secretion of mature IL1B and IL18.
“Importantly, multiple components of the molecular machinery for necroptosis—including ZBP1, RIPK3, MLKL, and TNFR1 (mainly via NF-κB)—impinge on the control of the so-called “inflammasome”, a supramolecular platform for the activation of CASP1 and consequent secretion of mature interleukin 1 beta (IL1B; best known as IL-1β) and IL18 [524–529].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [529]
Cites
Chen, Y., Wang, L., Kang, Q., Zhang, X., Yu, G., Wan, X., Wang, J., & Zhu, K. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477308 · Cited by 10,730 · see citing works
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066 · see citing works
The Pathophysiology and Treatment of Sepsis
Hotchkiss, R. S., & Karl, I. E. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021333 · Cited by 4,098 · see citing works
NF-κB regulation in the immune system
Li, Q., & Verma, I. M. (2002) · Nature Reviews Immunology · doi:10.1038/nri910 · Cited by 4,007 · see citing works
Missing Pieces in the NF-κB Puzzle
Ghosh, S., & Karin, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00703-1 · Cited by 3,638 · see citing works
Self-citationThe immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742 · see citing works
NF-κB at the crossroads of life and death
Karin, M., & Lin, A. (2002) · Nature Immunology · doi:10.1038/ni0302-221 · Cited by 2,709 · see citing works
Self-citationThe two NF-κB activation pathways and their role in innate and adaptive immunity
Bonizzi, G., & Karin, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.03.008 · Cited by 2,535 · see citing works
Self-citationIKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433 · see citing works
Self-citationConditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,143 · see citing works
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation
Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., Li, J. W., Young, D. B., Barbosa, M. S., Mann, M., Manning, A. M., et al. (1997) · Science · doi:10.1126/science.278.5339.860 · Cited by 2,042 · see citing works
Inducible Gene Targeting in Mice
Kühn, R., Schwenk, F., Aguet, M., & Rajewsky, K. (1995) · Science · doi:10.1126/science.7660125 · Cited by 1,915 · see citing works
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773 · see citing works
Self-citationvan Rooijen, N., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,763 · see citing works
Altered Cytokine Export and Apoptosis in Mice Deficient in Interleukin-1β Converting Enzyme
Kuida, K., Lippke, J. A., Ku, G., Harding, M. W., Livingston, D. J., Su, M. S. S., & Flavell, R. A. (1995) · Science · doi:10.1126/science.7535475 · Cited by 1,606 · see citing works
Failure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodolce, J. P., & Ma, A. (2000) · Science · doi:10.1126/science.289.5488.2350 · Cited by 1,409 · see citing works
Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C. G., McDowell, J., Paskind, M. P., Rodman, L., Salfeld, J. G., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90490-5 · Cited by 1,408 · see citing works
The IKK NF-κB system: a treasure trove for drug development
Karin, M., Yamamoto, Y., & Wang, Q. M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1279 · Cited by 1,364 · see citing works
Self-citationMaeda, S., Kamata, H., Luo, J., Leffert, H. L., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2005.04.014 · Cited by 1,165 · see citing works
Self-citationNeutrophil serine proteases: specific regulators of inflammation
Pham, C. T. N. (2006) · Nature reviews. Immunology · doi:10.1038/nri1841 · Cited by 1,017 · see citing works
Martinon, F., & Tschopp, J. (2004) · Cell · doi:10.1016/j.cell.2004.05.004 · Cited by 940 · see citing works
Innate Immunity Gone Awry: Linking Microbial Infections to Chronic Inflammation and Cancer
Karin, M., Lawrence, T., & Nizet, V. (2006) · Cell · doi:10.1016/j.cell.2006.02.016 · Cited by 938 · see citing works
Self-citationDisruption of Signaling by Yersinia Effector YopJ, a Ubiquitin-Like Protein Protease
Orth, K., Xu, Z., Mudgett, M. B., et al. (2000) · Science · doi:10.1126/science.290.5496.1594 · Cited by 549 · see citing works
Proinflammatory and Anti-inflammatory Cytokines as Mediators in the Pathogenesis of Septic Shock
Dinarello, C. A. (1997) · CHEST Journal · doi:10.1378/chest.112.6_supplement.321s · Cited by 508 · see citing works
Chen, L.-W., Egan, L. J., Li, Z.-W., Greten, F. R., Kagnoff, M. F., & Karin, M. (2003) · Nature Medicine · doi:10.1038/nm849 · Cited by 483 · see citing works
Self-citationThe Inflammasome: First Line of the Immune Response to Cell Stress
Ogura, Y., Sutterwala, F. S., & Flavell, R. A. (2006) · Cell · doi:10.1016/j.cell.2006.08.002 · Cited by 474 · see citing works
Interleukin 1 is processed and released during apoptosis.
Hogquist, K. A., Nett, M. A., Unanue, E. R., & Chaplin, D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.19.8485 · Cited by 456 · see citing works
The Serpin α1-Proteinase Inhibitor Is a Critical Substrate for Gelatinase B/MMP-9 In Vivo
Liu, Z., Zhou, X., Shapiro, S. D., Shipley, J. M., Twining, S. S., Diaz, L. A., Senior, R. M., & Werb, Z. (2000) · Cell · doi:10.1016/s0092-8674(00)00087-8 · Cited by 388 · see citing works
Black, R. A., Kronheim, S. R., Cantrell, M. A., Deeley, M. C., March, C. J., Prickett, K. S., Wignall, J. M., Conlon, P. J., Cosman, D. J., & Hopp, T. P. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)76559-4 · Cited by 380 · see citing works
Multiple biological activities of human recombinant interleukin 1.
Dinarello, C. A., Cannon, J. G., Mier, J. W., Bernheim, H. A., LoPreste, G., Lynn, D., Love, R. N., Webb, A. C., Auron, P. E., & Reuben, R. C. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112495 · Cited by 366 · see citing works
Coeshott, C. M., Ohnemus, C., Pilyavskaya, A., Ross, S., Wieczorek, M., Kroona, H., Leimer, A. H., & Cheronis, J. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.11.6261 · Cited by 365 · see citing works
Park, J. M., Greten, F. R., Wong, A. W., Westrick, R. J., Arthur, J. S. C., Otsu, K., Hoffmann, A., Montminy, M., & Karin, M. (2005) · Immunity · doi:10.1016/j.immuni.2005.08.010 · Cited by 320 · see citing works
Self-citationBcl-2 and Bcl-XL Regulate Proinflammatory Caspase-1 Activation by Interaction with NALP1
Bruey, J., Bruey-Sédano, N., Luciano, F., Zhai, D., Balpai, R., Xu, C., Kress, C. L., Bailly‐Maitre, B., Li, X., Osterman, A. L., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.045 · Cited by 319 · see citing works
Mizutani, H., Schechter, N. M., Lazarus, G. S., Black, R. A., & Kupper, T. S. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.4.821 · Cited by 317 · see citing works
Humke, E. W., Shriver, S. K., Starovasnik, M. A., Fairbrother, W. J., & Dixit, V. M. (2000) · Cell · doi:10.1016/s0092-8674(00)00108-2 · Cited by 270 · see citing works
Ruocco, M. G., Maeda, S., Park, J. M., Lawrence, T., Hsu, L.-C., Cao, Y., Schett, G., Wagner, E. F., & Karin, M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042081 · Cited by 252 · see citing works
Self-citationResponse to local inflammation of IL-1 beta-converting enzyme- deficient mice
Fantuzzi, G., Ku, G., Harding, M. W., Livingston, D. J., Sipe, J. D., Kuida, K., Flavell, R. A., & Dinarello, C. A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.4.1818 · Cited by 232 · see citing works
Granzyme A is an interleukin 1 beta-converting enzyme.
Irmler, M., Hertig, S., MacDonald, H. R., Sadoul, R., Becherer, J. D., Proudfoot, A. E. I., Solari, R. C. E., & Tschopp, J. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.5.1917 · Cited by 227 · see citing works
Processing of precursor interleukin 1 beta and inflammatory disease.
Hazuda, D. J., Strickler, J., Kueppers, F., Simon, P. L., & Young, P. R. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39328-7 · Cited by 217 · see citing works
McIntyre, K. W., Shuster, D. J., Gillooly, K. M., Dambach, D. M., Pattoli, M. A., Lu, P., Zhou, X., Qiu, Y., Zusi, F. C., & Burke, J. R. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11131 · Cited by 217 · see citing works
IKKβ Is Essential for Protecting T Cells from TNFα-Induced Apoptosis
Senftleben, U., Li, Z., Baud, V., & Karin, M. (2001) · Immunity · doi:10.1016/s1074-7613(01)00104-2 · Cited by 208 · see citing works
Self-citationSuffredini, A. F., Reda, D., Banks, S. M., Tropea, M., Agosti, J. M., & Miller, R. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.10.5038 · Cited by 205 · see citing works
Algül, H., Treiber, M., Lesina, M., Nakhai, H., Saur, D., Geisler, F., Pfeifer, A., Paxian, S. A., & Schmid, R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29882 · Cited by 194 · see citing works
Self-citationFailure of Lymphopoiesis after Adoptive Transfer of NF-κB–Deficient Fetal Liver Cells
Horwitz, B. H., Scott, M. L., Cherry, S. R., Bronson, R. T., & Baltimore, D. (1997) · Immunity · doi:10.1016/s1074-7613(00)80451-3 · Cited by 190 · see citing works
NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer
Kisseleva, T., Li, S., Vorontchikhina, M., Feirt, N. M., Kitajewski, J., & Schindler, C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27392 · Cited by 137 · see citing works
Essential Role for IκB Kinase β in Remodeling Carma1-Bcl10-Malt1 Complexes upon T Cell Activation
Wegener, E., Oeckinghaus, A., Papadopoulou, N., Lavitas, L.-M., Schmidt‐Supprian, M., Ferch, U., Mak, T. W., Ruland, J., Heissmeyer, V., & Krappmann, D. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.027 · Cited by 136 · see citing works
Monocyte Heterogeneity and Innate Immunity
Taylor, P. R., & Gordon, S. (2003) · Immunity · doi:10.1016/s1074-7613(03)00178-x · Cited by 135 · see citing works
Dinarello, C. A. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000185500.11080.91 · Cited by 134 · see citing works
Transient suppression of macrophage functions by liposome-encapsulated drugs
van Rooijen, N., Bakker, J., & Sanders, N. (1997) · Trends in biotechnology · doi:10.1016/s0167-7799(97)01019-6 · Cited by 116 · see citing works
Zingarelli, B. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000186079.88909.94 · Cited by 111 · see citing works
Vassiloyanakopoulos, A. P., Okamoto, S., & Fierer, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7676 · Cited by 101 · see citing works
Self-citationRapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKβ
Nagashima, K., Sasseville, V. G., Wen, D., Bielecki, A., Yang, H., Simpson, C., Grant, E. P., Hepperle, M. E., Harriman, G., Jaffee, B., et al. (2006) · Blood · doi:10.1182/blood-2005-09-3852 · Cited by 79 · see citing works
Self-citationWiesner, O., Litwiller, R. D., Hummel, A. M., Viss, M. A., McDonald, C. J., Jenne, D. E., Fass, D. N., & Specks, U. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.056 · Cited by 59 · see citing works
Shimohashi, N., Nakamuta, M., Uchimura, K., Sugimoto, R., Iwamoto, H., Enjoji, M., & Nawata, H. (2000) · Journal of Cellular Biochemistry · doi:10.1002/1097-4644(20000915)78:4 · Cited by 54 · see citing works
Miething, C., Grundler, R., Mugler, C., Brero, S., Hoepfl, J., Geigl, J. B., Speicher, M. R., Ottmann, O. G., Peschel, C., & Duyster, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604716104 · Cited by 53 · see citing works
Self-citationKannan-Thulasiraman, P., & Shapiro, D. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200379200 · Cited by 52 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755 · see citing works
Self-citationNF-κB signaling in inflammation
Liu, T., Zhang, L., Joo, D., & Sun, S.-C. (2017) · Signal Transduction and Targeted Therapy · doi:10.1038/sigtrans.2017.23 · Cited by 8,791 · see citing works
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationImmunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466 · see citing works
NF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679 · see citing works
Self-citationThe Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · see citing works
Crosstalk in NF-κB Signaling Pathways
Oeckinghaus, A., Hayden, M. S., & Ghosh, S. (2011) · Nature Immunology · doi:10.1038/ni.2065 · Cited by 1,942 · see citing works
NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., & Karin, M. (2008) · Nature · doi:10.1038/nature06905 · Cited by 1,614 · see citing works
Self-citationNF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria
Zhong, Z., Umemura, A., Sanchez-Lopez, E., Liang, S., Shalapour, S., Wong, J., He, F., Boassa, D., Perkins, G., Ali, S. R., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.057 · Cited by 1,197 · see citing works
Self-citationThe immunology of hepatocellular carcinoma
Ringelhan, M., Pfister, D., O’Connor, T., Pikarsky, E., & Heikenwalder, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0044-z · Cited by 1,076 · see citing works
IL-1 pathways in inflammation and human diseases
Gabay, C., Lamacchia, C., & Palmer, G. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.4 · Cited by 897 · see citing works
The inflammasome: an integrated view
Gross, O., Thomas, C. J., Guarda, G., & Tschopp, J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01046.x · Cited by 778 · see citing works
Resolution of Inflammation: What Controls Its Onset?
Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., & Teixeira, M. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00160 · Cited by 638 · see citing works
Sakurai, T., He, G., Matsuzawa, A., Yu, G.-Y., Maeda, S., Hardiman, G., & Karin, M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.06.016 · Cited by 487 · see citing works
Self-citationFang, H.-Y., Hughes, R., Murdoch, C., Coffelt, S. B., Biswas, S. K., Harris, A. L., Johnson, R. S., Imityaz, H. Z., Simon, M. C., Fredlund, E., et al. (2009) · Blood · doi:10.1182/blood-2008-12-195941 · Cited by 319 · see citing works
Self-citationInflammasome-independent regulation of IL-1-family cytokines
Netea, M. G., van de Veerdonk, F. L., van der Meer, J. W. M., Dinarello, C. A., & Joosten, L. A. B. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112306 · Cited by 326 · see citing works
NF-κB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer
Grinberg-Bleyer, Y., Oh, H., Desrichard, A., Bhatt, D. M., Caron, R., Chan, T. A., Schmid, R. M., Klein, U., Hayden, M. S., & Ghosh, S. (2017) · Cell · doi:10.1016/j.cell.2017.08.004 · Cited by 297 · see citing works
Self-citationNF-κB: a double-edged sword controlling inflammation
Liu, D., Zhong, Z., & Karin, M. (2022) · Biomedicines · doi:10.3390/biomedicines10061250 · Cited by 157 · see citing works
Self-citationLaparra, J. M., & Sanz, Y. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22459 · Cited by 131 · see citing works
Neutrophil-Derived IL-1β Impairs the Efficacy of NF-κB Inhibitors against Lung Cancer
McLoed, A. G., Sherrill, T. P., Cheng, D.-S., Han, W., Saxon, J. A., Gleaves, L. A., Wu, P., Polosukhin, V. V., Karin, M., Yull, F. E., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.085 · Cited by 107 · see citing works
Self-citationQin, Y., Liu, Y., Hao, W., Decker, Y., Tomic, I., Menger, M. D., Liu, C., & Fassbender, K. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600873 · Cited by 90 · see citing works
Critical Role for IL-18 in Spontaneous Lung Inflammation Caused by Autophagy Deficiency
Abdel Fattah, E., Bhattacharya, A., Herron, A., Safdar, Z., & Eissa, N. T. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402277 · Cited by 77 · see citing works
Subtype and Regional-Specific Neuroinflammation in Sporadic Creutzfeldt–Jakob Disease
Llorens, F., López-González, I., Thüne, K., Carmona, M., Zafar, S., Andréoletti, O., Zerr, I., & Ferrer, I. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00198 · Cited by 69 · see citing works
Effector functions of NLRs in the intestine: innate sensing, cell death, and disease
Yeretssian, G. (2012) · Immunologic Research · doi:10.1007/s12026-012-8317-3 · Cited by 37 · see citing works
- Authors
- Greten, F. R., Arkan, M. C., Bollrath, J., Hsu, L.-C., Goode, J., Miething, C., Göktuna, S. I., Neuenhahn, M., Fierer, J., Paxian, S., Van Rooijen, N., Xu, Y., O'Cain, T., Jaffee, B. B., Busch, D. H., Duyster, J., Schmid, R. M., Eckmann, L., & Karin, M.
- Affiliations
- TUM Klinikum (DE)
- University of California San Diego (US)
- Technical University of Munich (DE)
- Takeda Oncology (United States) (US)
- Corresponding author
- Greten, Florian R.
- Karin, Michael
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 130
- Issue
- 5
- Pages
- 918-931
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2134986
- OpenAlex
- W1992841021
- Cited by
- 616
- References
- 56
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 23 · 2023: 20 · 2022: 34 · 2021: 34 · 2020: 29 · 2019: 29 · 2018: 35 · 2017: 30 · 2016: 34 · 2015: 34 · 2014: 34 · 2013: 38 · 2012: 47
- FWCI
- 13.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2146 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- American Cancer Society
- Deutsche Forschungsgemeinschaft
- Technische Universität München
- Deutsche Krebshilfe
- U.S. Public Health Service (E06486)
- National Institute of Allergy and Infectious Diseases (AI56075, AI061712, R01AI056075, R01AI043477, AI 43477, R01AI061712, R37AI043477)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK70867, R01DK070867, P01DK035108, DK 35108)
- National Institute of Environmental Health Sciences (R01ES006376)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- NF-κB, IKKβ, IL-1β secretion, pro-IL-1β processing, caspase-1, serine protease, endotoxic shock, myeloid cells, macrophages, neutrophils, anti-inflammatory therapy, innate immunity, inflammation
- MeSH terms
- Animals, Carbolines, Cell Line, Disease Models, Animal, Humans, Lipopolysaccharides, Macrophages, Neutrophils, Niacinamide, RNA, Messenger, Serine Endopeptidases, Shock, Septic, Time Factors, Transfection, Tumor Necrosis Factor-alpha, Serpins, Interleukin-6, NF-kappa B, Apoptosis, Receptors, Interleukin-1, Mice, Knockout, Caspase 1, Neutrophil Infiltration, Protein Kinase Inhibitors, Mice, I-kappa B Kinase, Interleukin-1beta
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
