title: IL-17 contributes to cardiac fibrosis following experimental autoimmune myocarditis by a PKCβ/Erk1/2/NF-κB-dependent signaling pathway.
abstract: Myocarditis is a common clinical cardiovascular disease, and some patients progress to dilated cardiomyopathy (DCM) with chronic heart failure. Common viral infections are the most frequent cause of myocarditis, but other pathogens and autoimmune diseases have also been implicated. T(h)17 cells are novel IL-17-producing effector T helper cells that play an important role in the development of autoimmune myocarditis. Furthermore, IL-17 is also important in post-myocarditis cardiac remodeling and progression to DCM. However, the mechanisms whereby IL-17 and IL-17-producing cells promote the progression of cardiac fibrosis remain unclear. We therefore investigated whether IL-17 directly induced cardiac fibrosis in experimental autoimmune myocarditis (EAM) and explored the possible molecular mechanisms. The EAM model was induced and serum IL-17 level was detected by ELISA; western blot, immunofluorescence and sirius red staining were used to analyze the collagen expression. PCR was used to assay the IL-17RA and IL-17RC. The results indicated that IL-17 induced cardiac fibrosis both in vitro and in vivo. The protein kinase C (PKC)β/Erk1/2/NF-κB (Nuclear Factor κappa B) pathway was involved in the development of myocardial fibrosis and IL-17 contributed to cardiac fibrosis following EAM via this pathway. These results provide the first direct evidence for the involvement of the PKCβ/Erk1/2/NF-κB signaling pathway in IL-17-induced myocardial fibrosis.
authors.affiliation: Department of Immunology, Center of Clinical Medicine and Laboratory, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Liu
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.forename: Caixia
authors.initials: C
authors.lastname: Sun
authors.forename: Jingping
authors.initials: J
authors.lastname: Yin
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.forename: Siamak
authors.initials: S
authors.lastname: Sandoghchian
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiao
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology*; D024722:Cardiac Myosins / Q000008:administration & dosage; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000166:cytology / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D024722:Cardiac Myosins