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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


  • Chen LW
  • Egan L
  • Li ZW
  • Greten FR
  • Kagnoff MF
  • Karin M


Nature medicine

Publication Data

May 1, 2003

Associated Grants


Mesh Terms

  • 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