FAN stimulates TNF(alpha)-induced gene expression, leukocyte recruitment, and humoral response.
2009
Montfort, Anne | de Badts, Bénédicte | Douin-Echinard, Victorine | Martin, Pascal G.P. | Iacovoni, Jason, S. | Nevoit, Caroline | Therville, Nicole | Garcia, Virginie | Bertrand, Marie-Antoinette | Bessières, Marie-Hélène | Trombe, Marie-Claude | Levade, Thierry | Benoist, Hervé | Ségui, Bruno | Institut de médecine moléculaire de Rangueil (I2MR) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Laboratoire de Pharmacologie et Toxicologie ; Institut National de la Recherche Agronomique (INRA) | IFR 31 Louis Bugnard (IFR 31) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Faculté des Sciences Pharmaceutiques ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT) | Service de Parasitologie et Mycologie [CHU Toulouse] ; Institut Fédératif de Biologie (IFB) ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse] ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
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Afficher plus [+] Moins [-]anglais. 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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