Antagonistic action of IFN-beta and IFN-gamma on high affinity Fc gamma receptor expression in healthy controls and multiple sclerosis patients.
Monocyte-macrophage activation by IFN-gamma is characterized by a pronounced increase of high affinity Fc receptors for IgG (Fc gamma RI), capable of triggering respiratory burst, phagocytosis, Ab-dependent cytotoxicity, and release of proinflammatory cytokines. In view of the antagonism of IFN-beta on IFN-gamma action, of interest in the chronic inflammatory disorder multiple sclerosis, we examined the possible effect of IFN-beta on IFN-gamma induction of Fc gamma RI gene expression. We found that IFN-beta significantly down-regulated IFN-gamma-induced Fc gamma RI surface expression in peripheral blood monocytes from healthy donors, in a dose- and time-dependent manner. This down-regulation of Fc gamma RI surface levels did not correspond to a decrease in Fc gamma RI mRNA, suggesting a posttranscriptional effect of IFN-beta. Down-regulation of Fc gamma RI surface expression correlated with diminished cellular signaling through Fc gamma RI, since the IFN-gamma-induced increase in Fc gamma receptor-triggered respiratory burst was nearly completely abrogated by simultaneous addition of IFN-beta. Finally, the same antagonism between both IFNs on Fc gamma RI surface expression was observed in peripheral blood monocytes derived from multiple sclerosis patients; inhibition by IFN-beta was even increased (82+/-11%), as compared with healthy controls (67+/-4%). These results may partially help explain the beneficial effect of IFN-beta in multiple sclerosis.
Unité 365, Institut National de la Santé et de la Recherche Médicale, Institut Curie, Paris, France. u365@curie.fr
J
J
Van Weyenbergh
P
P
Lipinski
A
A
Abadie
D
D
Chabas
U
U
Blank
R
R
Liblau
J
J
Wietzerbin
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D016207:Cytokines; D008565:Membrane Proteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D016899:Interferon-beta; D007371:Interferon-gamma