IL-1 and tumor necrosis factor. Similarities and differences in stimulation of expression of alternative pathway of complement and IFN-beta 2/IL-6 genes in human fibroblasts.
IL-1 and TNF induced concentration-related increases in the synthesis of factor B, C3, and IFN-beta 2/IL-6 in human skin fibroblasts. Effects of both stimuli were apparent with concentrations as low as 0.1 ng/ml and maximal responses were observed between 1 and 10 ng/ml; only for IL-1 induction of IFN-beta 2/IL-6 was there a further increase in response up to 100 ng/ml. For factor B and C3, maximal increases induced by IL-1 and TNF were similar: 119- and 109-fold for factor B and 15-fold and 11-fold for C3, respectively. Although both IL-1 and TNF increase synthesis of factor B and C3 in hepatocytes, the increases observed in fibroblasts were approximately 50- and 8-fold more for factor B and C3, respectively. Neither protein synthesis nor mRNA for IFN-beta 2/IL-6 was present in HepG2 cells either before or after stimulation with IL-1 or TNF. In contrast to the similarities between the effects of IL-1 and TNF on synthesis of factor B, C3, and IFN-beta 2/IL-6, only TNF increased synthesis of factor H. Because TNF induces membrane IL-1 in fibroblasts, it is possible to speculate that the effects of TNF on fibroblasts are due to induction of IL-1. An autocrine action of TNF through IL-1 is possible for TNF-induced synthesis of IFN-beta 2/IL-6, but the effects of TNF on synthesis of factor B, C3, and factor H indicated that TNF has effects on fibroblasts separate from IL-1. The effects of IL-1 and TNF on the synthesis of factor B and C3 in fibroblasts may be a part of an acute phase response occurring at a local level. However, the large responses in synthesis of factor B and C3 to IL-1 and TNF may suggest that factor B and C3 have a role, as yet undescribed, in tissues in addition to the role these proteins are known to play in inflammation.
Katz
Y
Y
Division of Pulmonary Immunology, St. Louis Children's Hospital, MO 63110.
Strunk
R C
RC
D000328:Adult; D002460:Cell Line; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000235:genetics; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000235:genetics*; D007700:Kinetics; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D017242:Complement Factor H; D007371:Interferon-gamma; D011415:Complement Factor B