Gp130 signaling promotes development of acute experimental colitis by facilitating early neutrophil/macrophage recruitment and activation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Leif E SanderC Trautwein

Abstract

IL-6 is known to play a crucial role in the pathogenesis of chronic intestinal inflammation by modulating T cell functions. In this study, we investigated the role of gp130, the common signal transducer for all IL-6 cytokines, in a murine model of acute T cell independent colitis to better characterize the impact of gp130 on innate immune cells and the early stages of inflammation. Experimental colitis was induced by dextran sulfate sodium treatment of mice with inducible systemic deletion of gp130 (MxCre/gp130(-/-)), macrophage/neutrophil-specific gp130-deficiency (LysCre/gp130(-/-)), or bone marrow chimeric mice and compared with wild-type controls (gp130(f/f)). Systemic deletion of gp130 (MxCre/gp130(-/-)) protected mice from severe colitis and wasting and attenuated the mucosal inflammatory infiltrate as well as local cytokine, chemokine, and adhesion molecule expression. Experiments in newly generated macrophage/neutrophil-specific gp130-deleted animals (LysCre/gp130(-/-)) and gp130 bone marrow chimeric mice, revealed a dual mechanism of proinflammatory effects mediated by gp130. Leukocyte recruitment was impaired in gp130-deleted animals and gp130-deleted recipients of wild-type bone marrow, demonstrating a central role o...Continue Reading

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Citations

Jul 21, 2011·The Journal of Biological Chemistry·Takuya SuzukiSoichi Tanabe
Jul 9, 2010·Journal of Leukocyte Biology·J S Silver, C A Hunter
Dec 15, 2010·European Journal of Cell Biology·Jan SodenkampChristoph Hölscher
May 11, 2016·Pharmacological Reports : PR·René Galien
Feb 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sara Dutton SackettChristian Trautwein
Jan 7, 2018·The Journal of Experimental Medicine·Takahiro SekiYihai Cao
Jul 4, 2015·Immune Network·Hyemin KimWang Jae Lee
Mar 24, 2018·Physiological Genomics·Michael D SteuryNarayanan Parameswaran
Jan 11, 2020·Frontiers in Immunology·Keita IshisonoKohji Kitaguchi
Nov 17, 2009·Journal of Immunotoxicology·Nuria Olea-HerreroInés Díaz-Laviada
Aug 2, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guangwei LiuFei Han
Apr 24, 2018·The American Journal of Pathology·Sean W MateerSimon Keely

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