Modulation of IL-1-induced chemokine expression in human mesangial cells through alterations in redox status

The effects of altering intracellular redox potential on interleukin 1 (IL-I)-induced MCP-1 expression by human mesangial cells were examined, Thiol containing antioxidants significantly increased cellular glutathione content while decreasing glutathione disulfide levels, These antioxidants inhibited IL-T induction of MCP-1 mRNA expression, This correlated with a decrease in DIVA binding activity of NF-kappa B, a transcription factor thought to be necessary for MCP-I gene expression, Incubation of mesangial cells with the oxidizing agents diamide or hydrogen peroxide did not upregulate MCP-I gene expression, and prevented IL-I induction of MCP-I mRNA. Oxidants appeared to inhibit the degradation of I kappa B, and the translocation of NF-kappa B to the nucleus, Non-oxidative depletion of intracellular glutathione also attenuated the effects of IL-I on MCP-1 expression. These data indicate that tile intracellular redox potential is a critical determinant of cell activation by IL-1. The observation that both oxidizing and reducing environments are inhibitory suggests that redox changes fan affect the IL-l signal transduction pathway at multiple points. (C) 1997 Academic Press Limited.