FAN stimulates TNF(alpha)-induced gene expression, leukocyte recruitment, and humoral response.

Anne Montfort 1 Bénédicte De Badts 1 Victorine Douin-Echinard 1 Pascal Martin 2 Jason Iacovoni 3 Caroline Nevoit 3 Nicole Therville 1 Virginie Garcia 1 Marie-Antoinette Bertrand 4 Marie-Hélène Bessières 5 Marie-Claude Trombe 1 Thierry Levade 1 Hervé Benoist 1, 4 Bruno Ségui 1, 4, *
* Auteur correspondant
1 I2MR - Institut de médecine moléculaire de Rangueil
2 Laboratoire de Pharmacologie et Toxicologie
3 IFR 31 - IFR 31 Louis Bugnard
4 Service d'Immunologie
5 Service de Parasitologie-Mycologie [Toulouse]
Abstract : Factor associated with neutral sphingomyelinase activation (FAN) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression. Approximately 70% of TNF-induced genes exhibited lower expression levels in FAN-deficient than in wild-type fibroblasts. Of particular interest, TNF-induced expression of cytokines/chemokines, such as IL-6 and CXCL-2, was impaired in FAN-deficient cells. This was confirmed by real time RT-PCR and ELISA. Upon i.p. TNF or thioglycollate injection, neutrophil recruitment into the peritoneal cavity was reduced by more than 50% in FAN-deficient mice. Nevertheless, FAN-deficient animals did not exhibit an increased susceptibility to different microorganisms including bacteria and parasites, indicating that FAN is not essential for pathogen clearance. Specific Ab response to BSA was substantially impaired in FAN-deficient mice and this was associated with a reduced content of leukocytes in the spleen of BSA-challenged FAN-deficient mice as compared with their wild-type counterparts. Altogether, our results indicate the involvement of FAN in TNF-induced gene expression and leukocyte recruitment, contributing to the establishment of the specific immune response.
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Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 183 (8), pp.5369-78. 〈10.4049/jimmunol.0803384〉
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Contributeur : Marie Francoise Simon <>
Soumis le : vendredi 16 avril 2010 - 16:24:26
Dernière modification le : jeudi 13 septembre 2018 - 10:30:07

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Anne Montfort, Bénédicte De Badts, Victorine Douin-Echinard, Pascal Martin, Jason Iacovoni, et al.. FAN stimulates TNF(alpha)-induced gene expression, leukocyte recruitment, and humoral response.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 183 (8), pp.5369-78. 〈10.4049/jimmunol.0803384〉. 〈inserm-00473894〉

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