Pristane-induced arthritis loci interact with Slc11a1 gene to determine susceptibility in mice selected for high inflammation

Abstract

Event Abstract Back to Event Pristane-induced arthritis loci interact with Slc11a1 gene to determine susceptibility in mice selected for high inflammation Marcelo De Franco1*, Mara Correa1, Andrea Borrego1, José R. Jensen1, Wafa H. Cabrera1, Nancy Starobinas1, Orlando G. Ribeiro1, Antonella Galvan2, Tommaso A. Dragani2 and Olga M. Ibañez1 1 Instituto Butantan, Brazil 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Italy AIRmax (maximal inflammation) and AIRmin (minimal inflammation) mice show distinct susceptibility to pristane-induced arthritis (PIA). Slc11a1, which regulates macrophage and neutrophil activity, is involved in this disease. AIRmaxSS mice homozygous for the non-functional Slc11a1 S (gly169asp) allele are more susceptible than the other lines. The aim of this work was to identify genes in acute inflammatory reaction loci that interact with Slc11a1 alleles to modulate PIA. Mice received two ip injections of 0.5 mL pristane with 60 days of interval. Global gene expression analysis was performed on Affymetrix mouse 1.0 ST bioarrays (27k genes) using RNA (n=4) from arthritic or control paws. In parallel, genome wide linkage studies were performed to search for arthritis QTL in an F2 (AIRmax x AIRmin, n=290) population. Significant (LODscore > 4) arthritis QTL on chromosomes 5 and 8, and suggestive QTL on chromosomes 7, 17 and 19 were detected. Global gene expression analysis demonstrated significantly (P<0.001) over-represented genes related to inflammatory response and chemotaxis in AIRmaxRR and AIRmaxSS mice, as well as in the AIRmax heterozygous group. Higher up-regulation of chemokine genes Cxcl1, Cxcl9, Cxcl5, Cxcl13 on chromosome 5 was observed in AIRmaxSS than in the other lines. In chromosome 8, macrophage scavenger receptor 1 and heme oxigenase (decycling) 1 genes were also more expressed in AIRmaxSS mice. RT-qPCR experiments validated microarray analyses. Results revealed that the gene expression profile of two arthritis QTL (on chromosomes 5 and 8) correlates with Slc11a1 alleles, resulting in enhanced AIRmaxSS mice susceptibility to PIA. Acknowledgements Finantial Support: The State of São Paulo Research Foundation (FAPESP) and National Council of Research (CNPq), Brasil. Keywords: mice genetically selected, pristane-induced arthritis (PIA), global gene expression, QTL analysis, Inflammation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: De Franco M, Correa M, Borrego A, Jensen JR, Cabrera WH, Starobinas N, Ribeiro OG, Galvan A, Dragani TA and Ibañez OM (2013). Pristane-induced arthritis loci interact with Slc11a1 gene to determine susceptibility in mice selected for high inflammation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00419 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: 18 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Marcelo De Franco, Instituto Butantan, Sao Paulo, Brazil, mdfranco@butantan.gov.br 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 Marcelo De Franco Mara Correa Andrea Borrego José R Jensen Wafa H Cabrera Nancy Starobinas Orlando G Ribeiro Antonella Galvan Tommaso A Dragani Olga M Ibañez Google Marcelo De Franco Mara Correa Andrea Borrego José R Jensen Wafa H Cabrera Nancy Starobinas Orlando G Ribeiro Antonella Galvan Tommaso A Dragani Olga M Ibañez Google Scholar Marcelo De Franco Mara Correa Andrea Borrego José R Jensen Wafa H Cabrera Nancy Starobinas Orlando G Ribeiro Antonella Galvan Tommaso A Dragani Olga M Ibañez PubMed Marcelo De Franco Mara Correa Andrea Borrego José R Jensen Wafa H Cabrera Nancy Starobinas Orlando G Ribeiro Antonella Galvan Tommaso A Dragani Olga M Ibañez 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.