The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion.
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.
Pubmed ID: 12692538 RIS Download
Animals | Apoptosis | Gene Expression Regulation | I-kappa B Kinase | Inflammation | Intestines | Ischemia | Male | Mice | Mice, Inbred C57BL | Multiple Organ Failure | NF-kappa B | Protein-Serine-Threonine Kinases | Reperfusion Injury | Tumor Necrosis Factor-alpha