IL-17 A AND F ISOFORMS AND THEIR RECEPTORS IN EXPERIMENTAL CHOLESTASIS AND THE IL17A/F HETERODIMER INDUCES A PROFIBROGENIC PROFILE IN HEPATIC STELLATE CELLS IN VITRO

Abstract

Event Abstract Back to Event IL-17 A AND F ISOFORMS AND THEIR RECEPTORS IN EXPERIMENTAL CHOLESTASIS AND THE IL17A/F HETERODIMER INDUCES A PROFIBROGENIC PROFILE IN HEPATIC STELLATE CELLS IN VITRO Miriam R. Bueno-Topete1*, Sara M. Zepeda-Morales1, Susana Del Toro-Arreola1, Leonel Garcia2, Alejandra N. Vega-Magaña1, Blanca E. Bastidas-Ramírez1 and Mary Fafutis-Morris3 1 Universidad de Guadalajara, Biología Molecular y Genómica, Mexico 2 Universidad de Guadalajara, Fisiología, Mexico 3 Universidad de Guadalajara, Fisiología, Mexico Background. IL-17 plays a central role in the pathogenesis of fibrosis associated with various etiologies. Significant decrease in liver fibrosis in IL-17RA knockout mice has been demonstrated. However, the expression of IL-17 isoforms and their receptors in cholestatic liver fibrosis has not been explored yet. Aditionally, there is not enough information about IL-17A/F heterodimer in vitro signaling on hepatic stellate cells (HSC). Objetives. To analyze the expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in the liver of rats with cholestasis; aditionally we investigated the participation of IL-17A/F on HSC signaling. Methods. Male Wistar rats were sacrificed at 8 and 30d after bile duct ligation (BDL). Hepatic IL-17A, IL17-F, IL-17RA and IL-17RC expression was determined by qRT-PCR. Protein levels of IL-17 and RORgammaT were analyzed by Western Blot. Activated HSC were stimulated with IL-17A/F, then the transcriptional factors Stat-3p, NF-κB and Smad-2p and profibrogenic genes collagen I, III and TGF-beta were evaluated by qRT-PCR. Results. Hepatic gene expression of IL-17A, IL-17-F and IL-17RC dramatically increased at 8 and 30d post BDL. IL- 17RA significantly increased at 30d post BDL. The overall IL-17RC level was positively correlated with both IL-17A and IL-17F. At the protein level, IL-17 and RORgammaT significantly increased 8 and 30d post BDL. In vitro, Stat-3p, NF-kB, Smad-2p and collagen I, III and TGF-beta significantly increased in HSC stimulated with IL-17A/F. Conclusions. IL-17 (A and F) isoforms and their receptors are critical mediators of liver damage in experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17. Heterodimeric IL-17A/F potentially induces profibrogenic genes in HSC cultures. References Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, Cong M, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 2012; 143:765–76. Harada K, Shimoda S, Sato Y, Isse K, Ikeda H, Nakanuma Y. Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis. Clin Exp Immunol. 2009; 157:261–70. Keywords: IL-17 isoforms, liver fibrosis, RORγt, IL-17 RECEPTORS, Hepatic Stellate Cells Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Adaptive Immunity Citation: Bueno-Topete MR, Zepeda-Morales SM, Del Toro-Arreola S, Garcia L, Vega-Magaña AN, Bastidas-Ramírez BE and Fafutis-Morris M (2015). IL-17 A AND F ISOFORMS AND THEIR RECEPTORS IN EXPERIMENTAL CHOLESTASIS AND THE IL17A/F HETERODIMER INDUCES A PROFIBROGENIC PROFILE IN HEPATIC STELLATE CELLS IN VITRO. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00049 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Apr 2015; Published Online: 14 Sep 2015. * Correspondence: Prof. Miriam R Bueno-Topete, Universidad de Guadalajara, Biología Molecular y Genómica, Guadalajara, Jalisco, Mexico, ruthmyriamtop@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Miriam R Bueno-Topete Sara M Zepeda-Morales Susana Del Toro-Arreola Leonel Garcia Alejandra N Vega-Magaña Blanca E Bastidas-Ramírez Mary Fafutis-Morris Google Miriam R Bueno-Topete Sara M Zepeda-Morales Susana Del Toro-Arreola Leonel Garcia Alejandra N Vega-Magaña Blanca E Bastidas-Ramírez Mary Fafutis-Morris Google Scholar Miriam R Bueno-Topete Sara M Zepeda-Morales Susana Del Toro-Arreola Leonel Garcia Alejandra N Vega-Magaña Blanca E Bastidas-Ramírez Mary Fafutis-Morris PubMed Miriam R Bueno-Topete Sara M Zepeda-Morales Susana Del Toro-Arreola Leonel Garcia Alejandra N Vega-Magaña Blanca E Bastidas-Ramírez Mary Fafutis-Morris Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.