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: Eunok Im, Jane Jung, Sang Hoon Rhee
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 32 Issue 12 Pg. 583-91 (Dec 2012) ISSN: 1557-7465 [Electronic] United States
• PMID: 22994872 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Vesicular Transport
• IL17C protein, human
• Interleukin-17
• MYD88 protein, human
• Myeloid Differentiation Factor 88
• Neoplasm Proteins
• RNA, Messenger
• RNA, Small Interfering
• TICAM1 protein, human
• TLR5 protein, human
• Toll-Like Receptor 5
• Flagellin

Topics

• Adaptor Proteins, Vesicular Transport (antagonists & inhibitors, genetics, metabolism)
• Adenocarcinoma (immunology, metabolism)
• Cell Line
• Cell Line, Tumor
• Colitis, Ulcerative (immunology, metabolism)
• Colonic Neoplasms (immunology, metabolism)
• Crohn Disease (immunology, metabolism)
• Female
• Flagellin
• Gene Silencing
• Humans
• Interleukin-17 (biosynthesis, genetics, metabolism)
• Intestinal Mucosa (immunology, metabolism)
• Male
• Myeloid Differentiation Factor 88 (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Proteins (agonists, antagonists & inhibitors, genetics, metabolism)
• RNA, Messenger (metabolism)
• RNA, Small Interfering
• Toll-Like Receptor 5 (agonists, antagonists & inhibitors, genetics, metabolism)
• Up-Regulation