{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:13:33Z","timestamp":1774484013451,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2003,4,7]],"date-time":"2003-04-07T00:00:00Z","timestamp":1049673600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2003,5]]},"DOI":"10.1038\/nm849","type":"journal-article","created":{"date-parts":[[2003,4,30]],"date-time":"2003-04-30T18:05:09Z","timestamp":1051725909000},"page":"575-581","source":"Crossref","is-referenced-by-count":414,"title":["The two faces of IKK and NF-\u03baB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion"],"prefix":"10.1038","volume":"9","author":[{"given":"Lee-Wei","family":"Chen","sequence":"first","affiliation":[]},{"given":"Laurence","family":"Egan","sequence":"additional","affiliation":[]},{"given":"Zhi-Wei","family":"Li","sequence":"additional","affiliation":[]},{"given":"Florian R.","family":"Greten","sequence":"additional","affiliation":[]},{"given":"Martin F.","family":"Kagnoff","sequence":"additional","affiliation":[]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2003,4,7]]},"reference":[{"key":"BFnm849_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1146\/annurev.immunol.16.1.225","volume":"16","author":"S Ghosh","year":"1998","unstructured":"Ghosh, S., May, M.J. & Kopp, E.B. NF-\u03baB and Rel proteins: evolutionarily conserved mediators of immune responses. Ann. Rev. Immunol. 16, 225\u2013260 (1998).","journal-title":"Ann. Rev. Immunol."},{"key":"BFnm849_CR2","doi-asserted-by":"publisher","first-page":"S81","DOI":"10.1016\/S0092-8674(02)00703-1","volume":"109","author":"S Ghosh","year":"2002","unstructured":"Ghosh, S. & Karin, M. Missing pieces in the NF-\u03baB puzzle. Cell 109, S81\u2013S96 (2002).","journal-title":"Cell"},{"key":"BFnm849_CR3","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","volume":"336","author":"PJ Barnes","year":"1997","unstructured":"Barnes, P.J. & Karin, M. NF-\u03baB\u2014a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336, 1066\u20131071 (1997).","journal-title":"N. Engl. J. Med."},{"key":"BFnm849_CR4","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1172\/JCI119648","volume":"100","author":"H Bohrer","year":"1997","unstructured":"Bohrer, H. et al. Role of NF-\u03baB in the mortality of sepsis. J. Clin. Invest. 100, 972\u2013985 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFnm849_CR5","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1128\/IAI.68.4.1942-1945.2000","volume":"68","author":"F Arnalich","year":"2000","unstructured":"Arnalich, F. et al. Predictive value of NF-\u03baB activity and plasma cytokine levels in patients with sepsis. Infect. Immun. 68, 1942\u20131945 (2000).","journal-title":"Infect. Immun."},{"key":"BFnm849_CR6","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1177\/000313480006601002","volume":"66","author":"C Pennington","year":"2000","unstructured":"Pennington, C., Dunn, J., Li, C., Ha, T. & Browder, W. NF-\u03baB activation in acute appendicitis: a molecular marker for extent of disease? Am. J. Surg. 66, 914\u2013918 (2000).","journal-title":"Am. J. Surg."},{"key":"BFnm849_CR7","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1038\/nm1201-1291","volume":"7","author":"T Lawrence","year":"2001","unstructured":"Lawrence, T., Gilroy, D.W., Colville-Nash, P.R. & Willoughby, D.A. Possible new role for NF-\u03baB in the resolution of inflammation. Nat. Med. 7, 1291\u20131297 (2001).","journal-title":"Nat. Med."},{"key":"BFnm849_CR8","doi-asserted-by":"publisher","first-page":"6888","DOI":"10.1038\/sj.onc.1203236","volume":"18","author":"S Gerondakis","year":"1999","unstructured":"Gerondakis, S., Grossmann, M., Nakamura, Y., Pohl, T. & Grumont, R. Genetic approaches in mice to understand Rel\/NF-\u03baB and I\u03baB function: transgenics and knockouts. Oncogene 18, 6888\u20136895 (1999).","journal-title":"Oncogene"},{"key":"BFnm849_CR9","first-page":"RE1","volume":"1999 (5)","author":"DM Rothwarf","year":"1999","unstructured":"Rothwarf, D.M. & Karin, M. The NF-\u03baB activation pathway: a paradigm in information transfer from membrane to nucleus. Sci. STKE 1999 (5), RE1 (1999).","journal-title":"Sci. STKE"},{"key":"BFnm849_CR10","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1126\/science.284.5412.321","volume":"284","author":"Q Li","year":"1999","unstructured":"Li, Q., Van Antwerp, D., Mercurio, F., Lee, K.-F. & Verma, I.M. Severe liver degeneration in mice lacking the I\u03baB kinase 2 gene. Science 284, 321\u2013325 (1999a).","journal-title":"Science"},{"key":"BFnm849_CR11","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1126\/science.1073163","volume":"297","author":"JM Park","year":"2002","unstructured":"Park, J.M., Greten, F.R., Li, Z.-W. & Karin, M. Macrophage apoptosis by anthrax lethal factor and p38 MAP kinase inhibition. Science 297, 2048\u20132051 (2002).","journal-title":"Science"},{"key":"BFnm849_CR12","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/S0749-0704(05)70113-5","volume":"16","author":"RA Balk","year":"2000","unstructured":"Balk, R.A. Pathogenesis and management of multiple organ dysfunction or failure in severe sepsis and septic shock. Crit. Care Clin. 16, 337\u2013352 (2000).","journal-title":"Crit. Care Clin."},{"key":"BFnm849_CR13","first-page":"201","volume":"106","author":"DJ Schmeling","year":"1989","unstructured":"Schmeling, D.J., Caty, M.G., Oldham, K.T., Guice, K.S. & Hinshaw, D.B. Evidence for neutrophil-related acute lung injury after intestinal ischemia-reperfusion. Surgery 106, 201\u2013202 (1989).","journal-title":"Surgery"},{"key":"BFnm849_CR14","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6","volume":"190","author":"DL Carden","year":"2000","unstructured":"Carden, D.L. & Granger, D.N. Pathophysiology of ischaemia-reperfusion injury. J. Pathol. 190, 255\u2013266 (2000).","journal-title":"J. Pathol."},{"key":"BFnm849_CR15","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1097\/00000658-200105000-00010","volume":"233","author":"K Fukatsu","year":"2001","unstructured":"Fukatsu, K. et al. Enteral nutrition prevents remote organ injury and death after a gut ischemic insult. Ann. Surg. 233, 660\u2013668 (2001).","journal-title":"Ann. Surg."},{"key":"BFnm849_CR16","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1097\/00000658-199012000-00007","volume":"212","author":"MG Caty","year":"1990","unstructured":"Caty, M.G., Guice, K.S., Oldham, K.T., Remick, D.G. & Kunkel, S.I. Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. Ann. Surg. 212, 694\u2013700 (1990).","journal-title":"Ann. Surg."},{"key":"BFnm849_CR17","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/0092-8674(93)90134-C","volume":"73","author":"K Pfeffer","year":"1993","unstructured":"Pfeffer, K. et al. Mice deficient for the 55 kD tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73, 457\u2013467 (1993).","journal-title":"Cell"},{"key":"BFnm849_CR18","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/41493","volume":"388","author":"JA DiDonato","year":"1997","unstructured":"DiDonato, J.A., Hayakawa, M., Rothwarf, D.M., Zandi, E. & Karin, M. A cytokine-responsive I\u03baB kinase that activates the transcription factor NF-\u03baB. Nature 388, 548\u2013554 (1997).","journal-title":"Nature"},{"key":"BFnm849_CR19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1056\/NEJM198501173120305","volume":"312","author":"JM McCord","year":"1985","unstructured":"McCord, J.M. Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312, 159\u2013163 (1985).","journal-title":"N. Engl. J. Med."},{"key":"BFnm849_CR20","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1084\/jem.189.11.1839","volume":"189","author":"Z-W Li","year":"1999","unstructured":"Li, Z.-W. et al. The IKK\u03b2 subunit of I\u03baB kinase (IKK) is essential for NF-\u03baB activation and prevention of apoptosis. J. Exp. Med. 189, 1839\u20131845 (1999).","journal-title":"J. Exp. Med."},{"key":"BFnm849_CR21","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/S0092-8674(00)80153-1","volume":"86","author":"V Imbert","year":"1996","unstructured":"Imbert, V. et al. Tyrosine phosphorylation of I\u03baB\u03b1 activates NF-\u03baB without proteolytic degradation of I\u03baB\u03b1. Cell 86, 787\u2013798 (1996).","journal-title":"Cell"},{"key":"BFnm849_CR22","unstructured":"Li, Z.-W., Omori, S.A., Labuda, T., Karin, M. & Rickert, R.C. IKK\u03b2 is required for peripheral B cell proliferation and survival. J. Immunol. (in the press)."},{"key":"BFnm849_CR23","doi-asserted-by":"publisher","first-page":"6476","DOI":"10.1074\/jbc.274.10.6476","volume":"274","author":"D Pinto","year":"1999","unstructured":"Pinto, D., Robine, S., Jaisser, F., El Marjou, F.E. & Louvard, D. Regulatory sequences of the mouse villin gene that efficiently drive transgenic expression in immature and differentiated epithelial cells of small and large intestines. J. Biol. Chem. 274, 6476\u20136482 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFnm849_CR24","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1053\/gast.2001.21191","volume":"120","author":"A Nakajima","year":"2001","unstructured":"Nakajima, A. et al. Endogenous PPAR\u03b3 mediates anti-inflammatory activity in murine ischemia-reperfusion injury. Gastroenterology 120, 460\u2013469 (2001).","journal-title":"Gastroenterology"},{"key":"BFnm849_CR25","doi-asserted-by":"publisher","first-page":"L677","DOI":"10.1152\/ajplung.2001.281.3.L677","volume":"281","author":"Y Song","year":"2001","unstructured":"Song, Y. et al. A low level of TNF\u03b1 mediates hemorrhage-induced acute lung injury via p55 TNF receptor. Am. J. Physiol. Lung Cell. Mol. Physiol. 281, L677\u2013L684 (2001).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"BFnm849_CR26","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/S1097-2765(00)80262-2","volume":"15","author":"C Makris","year":"2000","unstructured":"Makris, C. et al. Female mice heterozygote for IKK\u03b3\/NEMO deficiencies develop a genodermatosis similar to the human X-linked disorder incontinentia pigmenti. Mol. Cell 15, 969\u2013979 (2000).","journal-title":"Mol. Cell"},{"key":"BFnm849_CR27","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1006\/meth.1996.0107","volume":"10","author":"SE Lewis","year":"1996","unstructured":"Lewis, S.E. & Konradi, C. Analysis of DNA-protein interactions in the nervous system using the electrophoretic mobility shift assay. Methods 10, 301\u2013311 (1996).","journal-title":"Methods"},{"key":"BFnm849_CR28","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1126\/science.284.5412.316","volume":"284","author":"Y Hu","year":"1999","unstructured":"Hu, Y. et al. Abnormal morphogenesis but intact IKK activation in mice lacking the IKK\u03b1 subunit of the I\u03baB kinase. Science 284, 316\u2013320 (1999).","journal-title":"Science"},{"key":"BFnm849_CR29","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1126\/science.1062677","volume":"293","author":"U Senftleben","year":"2001","unstructured":"Senftleben, U. et al. Activation by IKK\u03b1 of a second, evolutionary conserved, NF-\u03baB signaling pathway. Science 293, 1495\u20131499 (2001).","journal-title":"Science"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm849.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm849","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm849.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:34:01Z","timestamp":1684449241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,7]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,5]]}},"alternative-id":["BFnm849"],"URL":"https:\/\/doi.org\/10.1038\/nm849","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,7]]}}}