Sander, Leif E. and Obermeier, Florian and Dierssen, Uta and Kroy, Daniela C. and Singh, Anurag K. and Seidler, Ursula and Streetz, Konrad L. and Lutz, Holger H. and Mueller, Werner and Tacke, Frank and Trautwein, Christian (2008) Gp130 signaling promotes development of acute experimental colitis by facilitating early neutrophil/macrophage recruitment and activation. JOURNAL OF IMMUNOLOGY, 181 (5). pp. 3586-3594. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)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 gpl30 (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 gpl30 (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 gpl30 bone marrow chimeric mice, revealed a dual mechanism of proinflammatory effects mediated by gpl30. Leukocyte recruitment was impaired in gp130-deleted animals and gp130-deleted recipients of wild-type bone marrow, demonstrating a central role of gp130-dependent signals in nonmyeloid cells for directing leukocytes to sites of inflammation, which was further confirmed in a model of sterile peritonitis. In contrast, macrophage/neutrophil-specific gp130 deficiency delayed and attenuated the disease but only marginally affected the inflammatory infiltrate, indicating a defective activation of mucosal leukocytes. We provide evidence that IL-6 cytokines acting via gp130 are required in the acute stages of intestinal inflammation by modulating the dynamics of innate immune cell recruitment and activation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; SODIUM-INDUCED COLITIS; STAT3 ACTIVATION; INTESTINAL INFLAMMATION; LEUKOCYTE RECRUITMENT; MURINE COLITIS; CROHNS-DISEASE; T-CELLS; MICE; RECEPTOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 08:21 |
| Last Modified: | 26 Oct 2020 08:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30390 |
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