Interferon-gamma stimulates the secretion of IL-1, but not of IL-6, by glomerular mesangial cells

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Abstract
SUMMARY: IL-1 activity in culture supernatant and cell lysate from rat mesangial cells stimulated with interferon-gamma (IFN-γ) was measured by a thymocytc proliferation assay. While IFN-γ alone had no effect on the secretion or the intracellular pool of IL-1, the enhancement by IFN-γ of IL-1 secretion in response to lipopolysaccharide (LPS) was observed. The stimulatory effect of culture supernatant on thymocyte proliferation was abrogated by preincubation with the anti-IL-l antibody. At least 4–h incubation with IFN-γ and LPS was required to detect enhancing effect of I FN-γ. The addition of as little as 1 U/ml IFN-γ significantly increased IL-1 secretion in the presence of 10 μg/ml LPS. The IL-6 activity in culture supernatants was determined by measurement of thymidine uptake in mouse IL-6-dependent cell line (MH60.BSF2). Mesangial cells secreted IL-6 in culture supernatant without additional stimuli and LPS distinctly increased it as described previously. However, in contrast to IL-1 production, no effect of IFN-γ on IL-6 secretion was observed in the presence or absence of LPS. Moreover, we determined whether enhanced IL-1 release is associated with la expression on mesangial cells. IFN-γ alone and the combination with LPS induced marked expression of la antigen, whereas LPS alone did not. We conclude that IFN-γ stimulates the production of IL-1, but not IL-6, by mesangial cells and suggest an important role of IFN-γ in the pathogenesis of glomerulonephritis by regulating the mesangial production of IL-1 and the accessory cell function of mesangial cells.