Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts

• Published in: Journal of gastroenterology 2007-09, Vol.42 (9), p.746-753
• Main Authors: Yagi, Yuhki, Andoh, Akira, Inatomi, Osamu, Tsujikawa, Tomoyuki, Fujiyama, Yoshihide
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Blotting, Western; Cells, Cultured; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression; Humans; Interleukin-17 - pharmacology; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Intestinal Mucosa - secretion; Leukemia Inhibitory Factor - biosynthesis; Leukemia Inhibitory Factor - genetics; Matrix Metalloproteinase 1 - biosynthesis; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 3 - biosynthesis; Matrix Metalloproteinase 3 - genetics; RNA - genetics
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-007-2091-3

We investigated the potential role of interleukin (IL)-17 family members (IL-17A to IL-17F) in the induction of inflammatory responses in human colonic subepithelial myofibroblasts (SEMFs). The expression of the inflammatory cytokines IL-6, IL-8, leukemia inhibitory factor (LIF), and matrix metalloproteinases (MMP)-1 and MMP-3 were evaluated by enzyme-linked immunosorbent assay and Northern blotting. Activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-17A and IL-17F significantly enhanced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion. The effects of IL-17A were relatively stronger than those induced by IL-17F. The effects of IL-17B, IL-17C, IL-17D, and IL-17E were modest as compared with those induced by IL-17A and IL-17F. Both IL-17A and IL-17F augmented IL-1beta-induced secretion of IL-6, IL-8, LIF, MMP-1, and MMP-3. A similar augmentation was also observed in tumor necrosis factor (TNF)-alpha-induced cytokine and MMP secretion. IL-17A and IL-17F rapidly induced phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, p38 MAPKs, and c-Jun-NH(2)-terminal kinase (JNK) as early as 15 min after stimulation. Inhibitors for ERK (PD98059 and U0216) and p38 MAPK (SB203580) significantly reduced the IL-17F-induced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion. Among IL-17 family members, IL-17A and IL-17F strongly stimulate human colonic SEMFs, inducing inflammatory responses.