title: Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint.
abstract: Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells which plays critical role in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD) using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. IL-17 receptors were expressed in synovial fibroblasts as assessed using real-time PCR. Microarray analysis indicated that IL-17A treatment of synovial fibroblasts upregulated the expression of IL-6 and chemokines. Real-time PCR analysis showed that the gene expression of IL-6, CXCL1, IL-8, and CCL20 was significantly higher in IL-17A-treated synovial fibroblasts compared to nontreated controls. IL-6 protein production was increased by IL-17A in a time- and a dose-dependent manner. Additionally, IL-17A simulated IL-6 protein production in synovial fibroblasts samples isolated from three patients. Furthermore, signal inhibitor experiments indicated that IL-17-mediated induction of IL-6 was transduced via activation of NFκB and phosphatidylinositol 3-kinase/Akt. These results suggest that IL-17A is associated with the inflammatory progression of TMD.
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan; Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ogura
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan; Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Akutsu
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan; Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan; Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan.
authors.forename: Toshirou
authors.initials: T
authors.lastname: Kondoh
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D053722:Receptors, Interleukin-17 / Q000032:analysis; D015398:Signal Transduction; D013583:Synovial Membrane / Q000166:cytology* / Q000276:immunology; D013704:Temporomandibular Joint / Q000276:immunology*; D013705:Temporomandibular Joint Disorders / Q000209:etiology*
chemical_list: C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D053722:Receptors, Interleukin-17
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