title: Hypoxia inducible factor-1α-induced interleukin-33 expression in intestinal epithelia contributes to mucosal homeostasis in inflammatory bowel disease.
abstract: Intestinal epithelial cells (IECs), an important barrier to gut microbiota, are subject to low oxygen tension, particularly during intestinal inflammation. Hypoxia inducible factor-1α (HIF-1α) is expressed highly in the inflamed mucosa of inflammatory bowel disease (IBD) and functions as a key regulator in maintenance of intestinal homeostasis. However, how IEC-derived HIF-1α regulates intestinal immune responses in IBD is still not understood completely. We report here that the expression of HIF-1α and IL-33 was increased significantly in the inflamed mucosa of IBD patients as well as mice with colitis induced by dextran sulphate sodium (DSS). The levels of interleukin (IL)-33 were correlated positively with that of HIF-1α. A HIF-1α-interacting element was identified in the promoter region of IL-33, indicating that HIF-1α activity regulates IL-33 expression. Furthermore, tumour necrosis factor (TNF) facilitated the HIF-1α-dependent IL-33 expression in IEC. Our data thus demonstrate that HIF-1α-dependent IL-33 in IEC functions as a regulatory cytokine in inflamed mucosa of IBD, thereby regulating the intestinal inflammation and maintaining mucosal homeostasis.
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000818:Animals; D003092:Colitis / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D000067596:Interleukin-33 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C506536:IL33 protein, human; D000067596:Interleukin-33; D014409:Tumor Necrosis Factor-alpha
keywords: HIF-1α; IL-33; inflammatory bowel disease