Antagonistic action of IFN-beta and IFN-gamma on high affinity Fc gamma receptor expression in healthy controls and multiple sclerosis patients

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-30T13:24:01Z No. of bitstreams: 1 Van Weyenbergh J Antagonistic Action of....pdf: 94127 bytes, checksum: 84f1c90cf16e7fe9dcf404927c7e2f65 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-30T14:24:03Z (GMT) No. of bitstreams: 1 Van Weyenbergh J Antagonistic Action of....pdf: 94127 bytes, checksum: 84f1c90cf16e7fe9dcf404927c7e2f65 (MD5)Made available in DSpace on 2015-06-30T14:24:03Z (GMT). No. of bitstreams: 1 Van Weyenbergh J Antagonistic Action of....pdf: 94127 bytes, checksum: 84f1c90cf16e7fe9dcf404927c7e2f65 (MD5) Previous issue date: 1998Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / nstitut National de la Santé et de la Recherche Médicale (INSERM). Institut Curie. Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM). Institut Curie. Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM). Institut Curie. Paris, FranceHôpital Pitié-Salpêtrière. Fédération de Neurologie et INSERM. Laboratoire d’Immunologie Cellulaire. Paris, FranceInstitut Pasteur. Unité d’Immuno-Allergie. Paris, FranceHôpital Pitié-Salpêtrière. Fédération de Neurologie et INSERM. Laboratoire d’Immunologie Cellulaire. Paris, Francenstitut National de la Santé et de la Recherche Médicale (INSERM). Institut Curie. Paris, FranceMonocyte-macrophage activation by IFN-g is characterized by a pronounced increase of high affinity Fc receptors for IgG (FcgRI), capable of triggering respiratory burst, phagocytosis, Ab-dependent cytotoxicity, and release of proinflammatory cytokines. In view of the antagonism of IFN-b on IFN-g action, of interest in the chronic inflammatory disorder multiple sclerosis, we examined the possible effect of IFN-b on IFN-g induction of FcgRI gene expression. We found that IFN-b significantly downregulated IFN-g-induced FcgRI surface expression in peripheral blood monocytes from healthy donors, in a dose- and timedependent manner. This down-regulation of FcgRI surface levels did not correspond to a decrease in FcgRI mRNA, suggesting a posttranscriptional effect of IFN-b. Down-regulation of FcgRI surface expression correlated with diminished cellular signaling through FcgRI, since the IFN-g-induced increase in Fcg receptor-triggered respiratory burst was nearly completely abrogated by simultaneous addition of IFN-b. Finally, the same antagonism between both IFNs on FcgRI surface expression was observed in peripheral blood monocytes derived from multiple sclerosis patients; inhibition by IFN-b was even increased (82 6 11%), as compared with healthy controls (67 6 4%). These results may partially help explain the beneficial effect of IFN-b in multiple sclerosis