title: Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.
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.
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Jannie
authors.initials: J
authors.lastname: Pedersen
authors.affiliation: Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, K1H 8L1, Canada. Electronic address: eric@arc.cheo.ca.
authors.forename: Eric C
authors.initials: EC
authors.lastname: LaCasse
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Jakob B
authors.initials: JB
authors.lastname: Seidelin
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Ole H
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D055808:Drug Discovery; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D058990:Molecular Targeted Therapy; D005810:Multigene Family; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051034:Inhibitor of Apoptosis Proteins
keywords: anti-apoptotic proteins; inflammation; inflammatory bowel disease; intestine; signaling pathways; ubiquitin ligases