Hypoxia inducible factor-1α-induced interleukin-33 expression in intestinal epithelia contributes to mucosal homeostasis in inflammatory bowel disease

M. Sun, C. He, W. Wu, G. Zhou, F. Liu, Yingzi Cong, Z. Liu

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)428-440
    Number of pages13
    JournalClinical and Experimental Immunology
    Volume187
    Issue number3
    DOIs
    StatePublished - Mar 1 2017

    Fingerprint

    Hypoxia-Inducible Factor 1
    Intestinal Mucosa
    Inflammatory Bowel Diseases
    Homeostasis
    Epithelial Cells
    Mucous Membrane
    Inflammation
    Cell Hypoxia
    Dextran Sulfate
    Interleukin-33
    Colitis
    Genetic Promoter Regions
    Tumor Necrosis Factor-alpha
    Maintenance
    Cytokines
    Oxygen

    Keywords

    • HIF-1α
    • IL-33
    • inflammatory bowel disease

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Hypoxia inducible factor-1α-induced interleukin-33 expression in intestinal epithelia contributes to mucosal homeostasis in inflammatory bowel disease. / Sun, M.; He, C.; Wu, W.; Zhou, G.; Liu, F.; Cong, Yingzi; Liu, Z.

    In: Clinical and Experimental Immunology, Vol. 187, No. 3, 01.03.2017, p. 428-440.

    Research output: Contribution to journalArticle

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