Response of TNF-hyporesponsive SPRET/Ei mice in models of inflammatory disorders |
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Authors: | Jan Staelens Leen Puimège Tina Mahieu Gwenda Pynaert Tino Hochepied Annelies Vandenabeele Johan Grooten Dimitris Kontoyiannis Frans Van Roy George Kollias Claude Libert |
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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 |
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Abstract: | Most inflammatory disorders are becoming more prevalent, especially in Western countries. The proinflammatory cytokine tumor necrosis factor- (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, (B×S)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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