Enhanced synthesis of factor B induced by tumor necrosis factor in human skin fibroblasts is decreased by IL-4.
IL-4 is a T cell-derived lymphokine that has multiple biologic functions, affecting B cells, T cells, mast cells, monocytes, macrophages, and hematopoietic progenitor cells. We report that IL-4 also affects human skin fibroblasts. These effects were primarily in modulating the effects of other mediators of inflammation on these cells, with IL-4 producing little or no effects by itself. Synthesis of C proteins in human skin fibroblasts is modulated by TNF and other mediators of inflammation. TNF increased synthesis of factor B by 18.6-fold; IL-4 reduced the TNF effect on factor B synthesis by 83%. This effect started with concentrations of IL-4 as low as 0.1 ng/ml. The effect of IL-4 on the TNF-induced increase in synthesis of factor B occurred after 2 h incubation, the time when the effects of TNF alone were first observed. IL-4 also abrogated the effects of IL-1 and LPS on factor B synthesis, but did not affect the increase in synthesis of factor B induced by IFN-gamma. In contrast to the pattern for effect of IL-4 on factor B synthesis, the TNF-induced rate of synthesis of C3 was augmented by IL-4. The specificity of the IL-4 effect was also apparent when comparing the effect of IL-4 on the TNF-induced synthesis of factor B to the effects on total protein synthesis (increased 1.5-fold) and the TNF-induced increases in synthesis in C1r, C1s, C1 inhibitor, C2, and factor H (no changes). The IL-4-induced decrease in synthesis of factor B was mediated at a pretranslational level and was dependent on synthesis of a new protein. This interaction between IL-4 and mediators of inflammation can potentially modulate the inflammatory response in the setting of activation of Th cells.
Katz
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Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Strunk
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RC
D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis; D003180:Complement C3b Inactivator Proteins / Q000096:biosynthesis; D011415:Complement Factor B / Q000096:biosynthesis*; D017242:Complement Factor H; D003165:Complement System Proteins / Q000096:biosynthesis; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005347:Fibroblasts; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D004792:Enzyme Precursors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D017242:Complement Factor H; D007371:Interferon-gamma; D003165:Complement System Proteins; D011415:Complement Factor B