The two faces of IKK and NF-κB inhibition: prevention of systemic inflammation but increased local i
Author: ["Lee-Wei Chen","Laurence Egan","Zhi-Wei Li","Florian R. Greten","Martin F. Kagnoff","Michael Karin"]
Publication: Nature Medicine
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Abstract
We studied the role of NF-κB in acute inflammation caused by gut ischemia-reperfusion through selective ablation of IκB kinase (IKK)-β, the catalytic subunit of IKK that is essential for NF-κB activation. Ablation of IKK-β in enterocytes prevented the systemic inflammatory response, which culminates in multiple organ dysfunction syndrome (MODS) that is normally triggered by gut ischemia-reperfusion. IKK-β removal from enterocytes, however, also resulted in severe apoptotic damage to the reperfused intestinal mucosa. These results show the dual function of the NF-κB system, which is responsible for both tissue protection and systemic inflammation, and underscore the caution that should be exerted in using NF-κB and IKK inhibitors.
Cite this article
Chen, LW., Egan, L., Li, ZW. et al. The two faces of IKK and NF-κB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med 9, 575–581 (2003). https://doi.org/10.1038/nm849