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Nat Med. 2003 May;9(5):575-81. Epub 2003 Apr 7.

The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion.

Author information

1
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, California, USA.

Abstract

We studied the role of NF-kappaB in acute inflammation caused by gut ischemia-reperfusion through selective ablation of IkappaB kinase (IKK)-beta, the catalytic subunit of IKK that is essential for NF-kappaB activation. Ablation of IKK-beta in enterocytes prevented the systemic inflammatory response, which culminates in multiple organ dysfunction syndrome (MODS) that is normally triggered by gut ischemia-reperfusion. IKK-beta removal from enterocytes, however, also resulted in severe apoptotic damage to the reperfused intestinal mucosa. These results show the dual function of the NF-kappaB system, which is responsible for both tissue protection and systemic inflammation, and underscore the caution that should be exerted in using NF-kappaB and IKK inhibitors.

PMID:
12692538
DOI:
10.1038/nm849
[Indexed for MEDLINE]

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