Yagi, Y., Andoh, A., Inatomi, O., Tsujikawa, T. & Fujiyama, Y. Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts. J. Gastroenterol. 42, 746-753

Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, 520-2192, Japan.
Journal of Gastroenterology (Impact Factor: 4.52). 10/2007; 42(9):746-53. DOI: 10.1007/s00535-007-2091-3
Source: PubMed


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.

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    • "The secretion of matrix metalloproteinases (MMP1 and MMP3) is also enhanced under the influence of IL-17A and IL-17F (Yagi et al. 2007). IL-17B signals through an IL-17RB receptor and promotes tumorigenesis through NFκB dependent BCL2 expression in breast cancer cells (Huang et al. 2013). "
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    ABSTRACT: Interleukin-17 (IL-17) belongs to a relatively new family of cytokines that has garnered attention as the signature cytokine of Th17 cells. This cytokine family consists of 6 ligands, which bind to 5 receptor subtypes and induce downstream signaling. Although the receptors are ubiquitously expressed, cellular responses to ligands vary across tissues. The cytokine family is associated with various autoimmune disorders including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, asthma and psoriasis in addition to being implicated in the pathogenesis of cancer. In addition, this family plays a role in host defense against bacterial and fungal infections. The signaling mechanisms of the IL-17 family of proinflammatory cytokines are not well explored. In this study, we present a resource of literature-annotated reactions induced by IL-17. The reactions are catalogued under 5 categories, namely; molecular association, catalysis, transport, activation/inhibition and gene regulation. A total of 93 molecules and 122 reactions have been annotated. The IL-17 pathway is freely available through NetPath, a resource of signal transduction pathways previously developed by our group.
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    • "The persistent exposure to growing E. multilocularis metacestodes may have triggered the release of IL-17B by cells of the gastrointestinal tract, leading to the recruitment of neutrophil granulocytes into peri-parasite lesions. While the effects of IL-17B are similar to those mediated by TNF-α, IL-17A, and IL-1β, its potency is limited [39]. The IL-17B-induced infiltration of neutrophils into the peritoneal cavity in rats required much higher concentrations compared to TNF-α and it was still considerably less effective than the cell migration induced by IL-17A [38]. "
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    • "Of particular importance in the pathogenesis of RA is that IL-17 induces cartilage destruction via induction of metalloproteinases and inhibition of proteoglycan synthesis. IL-17 induces expression of RANKL on osteoblasts that mediates osteoclastogenesis, leading to bone destruction in RA.10,11 Regarding intestinal inflammation, IL-17 stimulated metalloproteinase, IL-6, and IL-8 production from cultured colonic subepithelial myofibroblasts.12 IL-17 also upregulates production of GM-CSF, IL-6, and GRO-α from keratinocytes.13 "
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    ABSTRACT: Until recently, autoimmune diseases had been categorized as either Th1- or Th2-mediated diseases. However, the discovery of a novel subset of helper T cells producing interleukin (IL)-17, ie, Th17 cells, changed this paradigm. Currently, IL-17 and Th17 cells are implicated in many autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Such conclusions were initially drawn from observations in animal models of autoimmune diseases, and accumulating data from clinical research also support the involvement of IL-17 in human diseases as well. Reagents targeting Th17-related molecules have been under clinical investigation for some diseases but have not always been effective in controlling disease activity. Consistent with this, it has become evident that there are substantial differences in the development of Th17 cells and in the way they function in autoimmune diseases between humans and experimental animals. Thus, further investigation is needed before we can draw any conclusions about the importance of IL-17 and Th17 cells in human autoimmune diseases.
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