Intramuscular administration of MMP-8 adenoviral vector reduces inflammation up-grade induced by vector delivery and allows prevention of liver fibrosis

Abstract

Event Abstract Back to Event Intramuscular administration of MMP-8 adenoviral vector reduces inflammation up-grade induced by vector delivery and allows prevention of liver fibrosis Jesus García-Bañuelos1*, Eden Oceguera-Contreras1, Daniela Gordillo-Bastidas1, Ana Sandoval-Rodríguez1, Blanca E. Bastidas-Ramírez2, Jaime González-Cuevas1, Jose Macias-Barragan1, 3, Belinda Gómez-Meda1 and Juan Armendariz-Borunda1, 4 1 Universidad de Guadalajara, Instituto de Biología Molecular en Medicina y Terapia Génica, CUCS., Mexico 2 Universidad de Guadalajara, Instituto de Enfermedades Crónico Degenerativas, CUCS., Mexico 3 Universidad de Guadalajara, Departamento de Ciencias Naturales y Exactas , CUValles., Mexico 4 OPD Hospital Civil de Guadalajara, Mexico BACKGROUND. Multiple protocols regarding liver fibrosis gene therapy using adenoviral vectors systemically delivered, have been reported. Unfortunately, a decrease in the efficiency of liver transduction and increase in proinflammatory cytokines have been exhibited when utilizing these delivering strategies. AIM. To establish a model to deliver therapeutic genes, focused in the prevention of liver fibrosis without promoting an inflammatory process by intramuscular administration using an adenoviral vector containing MMP8 gene (AdMMP8). MATERIAL AND METHODS. Experimental liver fibrosis was induced in male Wistar rats by TTA administration for 7 weeks. Four groups were included: control (no fibrosis), TAA induced-cirrhosis (TAA), TAA+AdGFP (irrelevant gene) and TAA+AdMMP8 (therapeutic gene). At the fifth week of TAA intoxication, administration of vectors in soleum muscle was accomplished. Subgroups of rats (n=5) at first, second and third week after vector administration were sacrificed. Percentage of fibrosis, liver function, MMP8 gene expression, proinflammatory (IL1β, TNFα), profibrogenic (COLIA1, TGFβ) and antifibrogenic (MMP1, MMP9) genes were determined. RESULTS. Liver and serum expression of MMP8 protein was sustained, fibrosis decreased up to 48%, proinflammatory genes expression was not modified, profibrogenic gene expression decreased, antifibrogenic genes expression increased, reduction of liver function was not statistically significant. According to Knodell score, intramuscular administration of AdMMP8, shows a diminishment of inflammatory cells infiltration in comparison with animals treated with AdGFP. CONCLUSION. AdMMP8 delivered in muscle did not generate liver inflammation in fibrotic animals, MMP8 gene was expressed in muscle with satisfactory functions in the liver. Acknowledgements This work was supported by a grant from CONACYT to Jesus Garcia-Bañuelos No. 25480 and CONACYT to Juan Armendáriz- Borunda No. 25474. Keywords: liver inflammation, Gene Therapy, viral vectors, inflammatory cytokines, TNFa Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: García-Bañuelos J, Oceguera-Contreras E, Gordillo-Bastidas D, Sandoval-Rodríguez A, Bastidas-Ramírez BE, González-Cuevas J, Macias-Barragan J, Gómez-Meda B and Armendariz-Borunda J (2013). Intramuscular administration of MMP-8 adenoviral vector reduces inflammation up-grade induced by vector delivery and allows prevention of liver fibrosis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00235 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: 13 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Jesus García-Bañuelos, Universidad de Guadalajara, Instituto de Biología Molecular en Medicina y Terapia Génica, CUCS., Guadalajara, Mexico, bgarcia@cucs.udg.mx 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 Jesus García-Bañuelos Eden Oceguera-Contreras Daniela Gordillo-Bastidas Ana Sandoval-Rodríguez Blanca E Bastidas-Ramírez Jaime González-Cuevas Jose Macias-Barragan Belinda Gómez-Meda Juan Armendariz-Borunda Google Jesus García-Bañuelos Eden Oceguera-Contreras Daniela Gordillo-Bastidas Ana Sandoval-Rodríguez Blanca E Bastidas-Ramírez Jaime González-Cuevas Jose Macias-Barragan Belinda Gómez-Meda Juan Armendariz-Borunda Google Scholar Jesus García-Bañuelos Eden Oceguera-Contreras Daniela Gordillo-Bastidas Ana Sandoval-Rodríguez Blanca E Bastidas-Ramírez Jaime González-Cuevas Jose Macias-Barragan Belinda Gómez-Meda Juan Armendariz-Borunda PubMed Jesus García-Bañuelos Eden Oceguera-Contreras Daniela Gordillo-Bastidas Ana Sandoval-Rodríguez Blanca E Bastidas-Ramírez Jaime González-Cuevas Jose Macias-Barragan Belinda Gómez-Meda Juan Armendariz-Borunda 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.