A quantitative trait loci analysis to map genes involved in lipopolysaccharide-induced inflammatory response: identification of macrophage scavenger receptor 1 as a candidate gene

The Journal of Immunology : Official Journal of the American Association of Immunologists
William B FultonAntonio De Maio

Abstract

Septic shock, which is a major complication observed after trauma and other human diseases, is likely the product of a prolonged and poorly controlled systemic inflammatory response. Symptoms of sepsis can be partially reproduced by injection of bacterial LPS in mice. Differences in mortality between C57BL/6J(high) and A/J(low) mice after LPS injection have been previously observed and correlated with differences in the inflammatory response between these two inbred strains. In the present study, we have mapped four loci responsible for differences in levels of LPS-induced IL-10, named modifier of IL-10, between the two strains. A locus within mouse chromosome 8 was confirmed using chromosome 8 consomic mice. This locus was further reduced in size by haplotype analysis and evaluated by the presence of potential candidate genes. The macrophage scavenger receptor 1 (Msr1) within this locus emerged as a candidate gene based on differences at the expression and structural levels between C57BL/6J and A/J mice. In comparison with wild-type (C57BL/6J) mice, Msr1 knockout mice displayed reduced levels of LPS-induced IL-10, but not of TNF-alpha or IL-6, confirming a specific role for this gene in the regulation of IL-10. These results s...Continue Reading

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Citations

Nov 26, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Szczepan JózefowskiLester Kobzik
Apr 23, 2009·The Journal of International Medical Research·Q XiangJ Tian
Jul 2, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Ivana V YangDavid A Schwartz
Oct 2, 2009·European Journal of Immunology·Martin BeisiegelStefan H E Kaufmann
Nov 16, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Huanfa YiXiang-Yang Wang
Apr 21, 2012·The Journal of Biological Chemistry·David M CauviAntonio De Maio
Aug 13, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jie QianXiang-Yang Wang
Jan 10, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcella FerlitoCharles Steenbergen
Dec 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Tracie A SeimonIra Tabas
Apr 9, 2011·The Journal of Surgical Research·Robert DrummondAntonio De Maio

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