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.

Abstract

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.

• Authors: Y Katz, R C Strunk
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 142 Issue 11 Pg. 3862-7 (Jun 01 1989) ISSN: 0022-1767 [Print] United States
• PMID: 2523936 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CFH protein, human
• Complement C3
• Complement C3b Inactivator Proteins
• Interleukin-1
• Interleukin-6
• Interleukins
• Tumor Necrosis Factor-alpha
• Dexamethasone
• Complement Factor H
• Interferon-gamma
• Complement Factor B

Topics

• Adult
• Cell Line
• Complement Activation (drug effects)
• Complement C3 (genetics)
• Complement C3b Inactivator Proteins (metabolism)
• Complement Factor B (genetics)
• Complement Factor H
• Complement Pathway, Alternative (drug effects)
• Dexamethasone (pharmacology)
• Female
• Fibroblasts (metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Interferon-gamma (pharmacology)
• Interleukin-1 (pharmacology)
• Interleukin-6
• Interleukins (genetics)
• Kinetics
• Male
• Tumor Necrosis Factor-alpha (pharmacology)