Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation

Trends Mol Med. 2014 Nov;20(11):652-65. doi: 10.1016/j.molmed.2014.09.006. Epub 2014 Oct 1.

Abstract

The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential.

Keywords: anti-apoptotic proteins; inflammation; inflammatory bowel disease; intestine; signaling pathways; ubiquitin ligases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Drug Discovery
  • Humans
  • Immunity, Innate
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestines / immunology*
  • Molecular Targeted Therapy
  • Multigene Family
  • Signal Transduction / drug effects

Substances

  • Inhibitor of Apoptosis Proteins