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Response of TNF-hyporesponsive SPRET/Ei mice in models of inflammatory disorders
Authors:Jan Staelens  Leen Puimège  Tina Mahieu  Gwenda Pynaert  Tino Hochepied  Annelies Vandenabeele  Johan Grooten  Dimitris Kontoyiannis  Frans Van Roy  George Kollias  Claude Libert
Affiliation:(1) Unit for Molecular Genetics in the Mouse, Department of Molecular Biomedical Research, Ghent University-Flanders Interuniversity Institute for Biotechnology, Zwijnaarde, Belgium;(2) Unit for Molecular Immunology, Department of Molecular Biomedical Research, Ghent University-Flanders Interuniversity Institute for Biotechnology, Zwijnaarde, Belgium;(3) Laboratory of Molecular Genetics, Alexander Fleming Biomedical Sciences Research Institute, Vari, Greece
Abstract:Most inflammatory disorders are becoming more prevalent, especially in Western countries. The proinflammatory cytokine tumor necrosis factor-agr (TNF) plays a prominent role in many of these inflammatory disorders. We have previously shown that SPRET/Ei mice exhibit an extreme and dominant resistance to high doses of TNF. In this report, we investigate the response of heterozygous (C57BL/6xSPRET/Ei)F1 mice in different models of inflammatory diseases. Compared with C57BL/6 mice, (Bthinsp×thinspS)F1 mice are protected against TNF-induced arthritis and are partially protected against allergic asthma in an ovalbumin-induced model. However, these mice display complete susceptibility to TNF-induced inflammatory bowel disease. These results indicate that the SPRET/Ei genome harbors potent dominant antiinflammatory genes that might be relevant for the treatment of certain chronic inflammatory diseases. It is very well possible that different genes are implicated in the different models.
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