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http://purl.uniprot.org/citations/26752465http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26752465http://www.w3.org/2000/01/rdf-schema#comment"

Background

Interleukin (IL)-36 (IL-36α, IL-36β, and IL-36γ) is a recently reported member of the IL-1 cytokine family. In this study, we investigated IL-36 expression in the inflamed mucosa of patients with inflammatory bowel disease and characterized the proinflammatory actions of IL-36 cytokines in human colonic epithelial cells.

Methods

IL-36 mRNA expression was evaluated using real-time PCR. IL-36 protein expression was analyzed using immunoblotting and immunohistochemical technique. Intracellular signaling pathways were evaluated by immunoblotting and by specific siRNA-transfected cells.

Results

The mRNA expression of IL-36α and IL-36γ, but not of IL-36β, was enhanced in the inflamed mucosa of patients with inflammatory bowel disease, in particular, in ulcerative colitis. Immunohistochemical analysis showed that T cells, monocytes, and plasma cells are the source of IL-36α and IL-36γ in colonic mucosa. DNA microarray analysis indicated that IL-36α induces the mRNA expression of CXC chemokines and acute phase proteins in intestinal epithelial cell line, HT-29 cells. IL-36α and IL-36γ dose-dependently and time-dependently induced the mRNA and protein expression of CXC chemokines (CXCL1, CXCL2, CXCL3 etc.) in HT-29 and Widr cells. Stimulation with IL-36α and IL-36γ assembled MyD88 adaptor proteins (MyD88, TRAF6, IRAK1, and TAK1) into a complex and induced the activation of NF-κB and AP-1 and also the phosphorylation of MAPKs. MAPK inhibitors and siRNAs specific for NF-κB and c-Jun AP-1 significantly reduced IL-36-induced CXC chemokine expression.

Conclusions

IL-36α and IL-36γ may play a proinflammatory role in the pathophysiology of inflammatory bowel disease through induction of CXC chemokines and acute phase proteins."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.org/dc/terms/identifier"doi:10.1097/mib.0000000000000654"xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Kanda T."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Sugimoto M."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Hidaka K."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Nishida A."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Andoh A."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Shioya M."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Kitoh K."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Bamba S."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Inatomi O."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/author"Imaeda H."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/name"Inflamm Bowel Dis"xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/pages"303-314"xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/title"Increased Expression of Interleukin-36, a Member of the Interleukin-1 Cytokine Family, in Inflammatory Bowel Disease."xsd:string
http://purl.uniprot.org/citations/26752465http://purl.uniprot.org/core/volume"22"xsd:string
http://purl.uniprot.org/citations/26752465http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26752465
http://purl.uniprot.org/citations/26752465http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26752465
http://purl.uniprot.org/uniprot/#_Q9UHA7-mappedCitation-26752465http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26752465
http://purl.uniprot.org/uniprot/Q9UHA7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/26752465