title: Toll-like receptor 5 engagement induces interleukin-17C expression in intestinal epithelial cells.
abstract: The family of interleukin-17 (IL-17) cytokine is the essential inflammatory mediator that influences the pathophysiology of various inflammatory diseases. Many studies focused on investigating the expression, signaling, and biological impacts of IL-17A and IL-17F, and the neutralization of these cytokines exhibited some promising results in clinical trials. In contrast, the expression resources and physiological relevance of IL-17C remained to be studied. In this study, through a microarray approach conducted with nontransformed human colonic epithelial cells (NCM460), we found that bacterial flagellin stimulation elicited potent IL-17C mRNA expression. We also confirmed that IL-17C protein production was strongly induced by flagellin in these cells. Flagellin-induced IL-17C expression was also observed in human colon adenocarcinoma cells such as DLD-1 and HT-29, indicating that IL-17C could be a signature inflammatory cytokine from intestinal epithelial cells in response to flagellin. Since inhibited in TLR5-, or MyD88- or TRIF-silenced cells, flagellin-induced IL-17C expression was specifically mediated by TLR5 and, subsequently, MyD88 and TRIF adaptor molecules. Furthermore, in line with inflammatory nature of IL-17, we found that IL-17C expression was substantially enhanced in the intestinal tissues from Ulcerative colitis patients. Given the facts that TLR5 is a key pattern recognition receptor which mediates microbial recognition in the intestinal epithelium and IL-17C turned out to be a unique member of the IL-17 family expressed in intestinal epithelial cells on TLR5 activation, our study may provide an important clue on understanding how intestinal microbes would contribute to an inflammatory program in the gut.
authors.affiliation: School of Pharmacy, Pusan National University, Busan, Korea.
authors.forename: Eunok
authors.initials: E
authors.lastname: Im
authors.forename: Jane
authors.initials: J
authors.lastname: Jung
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Rhee
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D005260:Female; D005408:Flagellin; D020868:Gene Silencing; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051198:Toll-Like Receptor 5 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C515925:IL17C protein, human; D020381:Interleukin-17; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C470409:TICAM1 protein, human; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin