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Response of TNF-hyporesponsive SPRET/Ei mice in models of inflammatory disorders

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Abstract

Most inflammatory disorders are becoming more prevalent, especially in Western countries. The proinflammatory cytokine tumor necrosis factor-α (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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Abbreviations

OVA:

chicken ovalbumin

PBS:

phosphate buffered saline

TNF:

tumor necrosis factor alpha

RA:

rheumatoid arthritis

IBD:

inflammatory bowel disease

TD:

tissue destruction

BAL:

brochoalveolar lavage

BALF:

BAL fluid

B:

C57BL/6

S:

SPRET/Ei

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Acknowledgments

This work was supported in part by the Fonds voor Wetenschappelijk Onderzoek–Vlaanderen (Grant G023698N), the Interuniversitaire attractiepolen, and FORTIS assurancies. J.S., T.M., and A.V. are fellows with the Vlaamse Instituut voor de bevordering van het Wetenschappelijk–Technologisch Onderzoek in de Industrie.

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Authors and Affiliations

  1. Unit for Molecular Genetics in the Mouse, Department of Molecular Biomedical Research, Ghent University-Flanders Interuniversity Institute for Biotechnology, Zwijnaarde, Belgium

    Jan Staelens, Leen Puimège, Tina Mahieu, Tino Hochepied, Annelies Vandenabeele, Frans Van Roy & Claude Libert

  2. Unit for Molecular Immunology, Department of Molecular Biomedical Research, Ghent University-Flanders Interuniversity Institute for Biotechnology, Zwijnaarde, Belgium

    Gwenda Pynaert

  3. Laboratory of Molecular Genetics, Alexander Fleming Biomedical Sciences Research Institute, Vari, Greece

    Johan Grooten, Dimitris Kontoyiannis & George Kollias

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  1. Jan Staelens
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  2. Leen Puimège
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  3. Tina Mahieu
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  10. George Kollias
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  11. Claude Libert
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Correspondence to Claude Libert.

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Staelens, J., Puimège, L., Mahieu, T. et al. Response of TNF-hyporesponsive SPRET/Ei mice in models of inflammatory disorders. Mamm Genome 15, 537–543 (2004). https://doi.org/10.1007/s00335-004-3002-z

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  • DOI: https://doi.org/10.1007/s00335-004-3002-z

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