Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint

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...

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Main Authors: Toshio Hattori, Naomi Ogura, Miwa Akutsu, Mutsumi Kawashima, Suguru Watanabe, Ko Ito, Toshirou Kondoh
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/436067
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author Toshio Hattori
Naomi Ogura
Miwa Akutsu
Mutsumi Kawashima
Suguru Watanabe
Ko Ito
Toshirou Kondoh
author_facet Toshio Hattori
Naomi Ogura
Miwa Akutsu
Mutsumi Kawashima
Suguru Watanabe
Ko Ito
Toshirou Kondoh
author_sort Toshio Hattori
collection DOAJ
description 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.
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spelling doaj-art-8263dcdba8cf4f46851339fd09a84fe02025-02-03T01:13:13ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/436067436067Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular JointToshio Hattori0Naomi Ogura1Miwa Akutsu2Mutsumi Kawashima3Suguru Watanabe4Ko Ito5Toshirou Kondoh6Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanDepartment of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanDepartment of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanDepartment of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanDepartment of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanDepartment of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanDepartment of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, JapanSynovial 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.http://dx.doi.org/10.1155/2015/436067
spellingShingle Toshio Hattori
Naomi Ogura
Miwa Akutsu
Mutsumi Kawashima
Suguru Watanabe
Ko Ito
Toshirou Kondoh
Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint
Mediators of Inflammation
title Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint
title_full Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint
title_fullStr Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint
title_full_unstemmed Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint
title_short Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint
title_sort gene expression profiling of il 17a treated synovial fibroblasts from the human temporomandibular joint
url http://dx.doi.org/10.1155/2015/436067
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