Stimulation of macrophage synthesis of complement C1q by interferon-gamma mediated by endogenous interferon-alpha/beta.
Both exogenous interferon-gamma (IFN-gamma) and interferon-alpha/beta (IFN-alpha/beta) stimulate C1q mRNA synthesis in murine macrophages. Previous studies suggested that IFN-gamma induced endogenous synthesis of IFN-alpha/beta by murine macrophages. In the present study, we determined the indirect effect of IFN-gamma on macrophage synthesis of C1q mRNA mediated by endogenous IFN-alpha/beta production. Upregulation of macrophage synthesis of C1q mRNA by both IFN-gamma and IFN-alpha/beta was reversed by neutralizing antibody to IFN-alpha/beta but not by nonimmune control serum. IFN-gamma was confirmed by ELISA to stimulate a six- to eightfold increase in macrophage secretion of IFN-alpha/beta compared with untreated control cells. We tentatively conclude that IFN-gamma stimulates macrophage synthesis and secretion of IFN-alpha/beta, which in turn promotes C1q mRNA synthesis in an autocrine or paracrine manner. Thus, exogenous IFN-gamma, derived from activated T lymphocytes, may act primarily on the macrophage to stimulate the endogenous synthesis of IFN-alpha/beta for autocrine modulation of a variety of biologic functions, including C1q synthesis.
Kolosov
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Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104-5046, USA.
Kolosova
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D000818:Animals; D000937:Antigen-Antibody Reactions; D001483:Base Sequence; D015922:Complement C1q / Q000096:biosynthesis* / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D013268:Stimulation, Chemical; D015854:Up-Regulation
D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; D015922:Complement C1q; D007371:Interferon-gamma