Transforming growth factor beta modulates C3 and factor B biosynthesis and complement receptor 3 expression in cultured human monocytes.
Complement biosynthesis in monocytes is stimulated by different pathogens and modulated by a variety of cytokines, but little is known about the possible effect of transforming growth factor beta (TGF-beta) on this monocyte function. We therefore studied the effect of TGF-beta 1 and TGF-beta 2 on constitutive, lipopolysaccharide (LPS)- and Candida albicans-induced monocyte biosynthesis of complement components C3 and factor B. Under all three conditions, both forms of TGF-beta (20 ng/ml) induced a two- to fourfold increase in C3 concentration in monocyte supernatants harvested after 2 or 5 days of cell culture, an effect that was abrogated by cycloheximide. In contrast, constitutive and pathogen-induced production of factor B was suppressed by TGF-beta. The effects of TGF-beta on complement production were neutralized by a monoclonal anti-TGF-beta antibody. Moreover, TGF-beta suppressed the pathogen-induced release of granulocyte-macrophage colony-stimulating factor and down-regulated the expression of complement receptor 3 (CD11b/CD18), while the expression of CD11a/CD18, a related beta 2 integrin, was unaffected. These novel effects of TGF-beta emphasize the immunomodulatory significance of this cytokine.
Department of Pediatric Research, National Hospital, Oslo, Norway.
A K
AK
Høgåsen
K
K
Hestdal
K
K
Høgåsen
T G
TG
Abrahamsen
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000954:Antigens, Surface / Q000032:analysis; D002176:Candida albicans / Q000187:drug effects; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis*; D011415:Complement Factor B / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010641:Phenotype; D011951:Receptors, Complement / Q000096:biosynthesis*; D012636:Secretory Rate / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000954:Antigens, Surface; D003176:Complement C3; D008070:Lipopolysaccharides; D011951:Receptors, Complement; D016212:Transforming Growth Factor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D011415:Complement Factor B