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-1)-induced MCP-1 gene expression by human mesangial cells were examined. Thiol containing antioxidants significantly increased cellular glutathione content while decreasing glutathione disulfide levels. These antioxidants inhibited IL-1 induction of MCP-1 mRNA expression. This correlated with a decrease in DNA binding activity of NF-kappa B, a transcription factor thought to be necessary for MCP-1 gene expression. Incubation of mesangial cells with the oxidizing agents diamide or hydrogen peroxide did not upregulate MCP-1 gene expression, and prevented IL-1 induction of MCP-1 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-1 on MCP-1 expression. These data indicate that the 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 can affect the IL-1 signal transduction pathway at multiple points.
Rovin
B H
BH
Department of Medicine, Ohio State University School of Medicine, Columbus 43210, USA.
Dickerson
J A
JA
Tan
L C
LC
Fassler
J
J
D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003958:Diamide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000975:Antioxidants; D018932:Chemokine CCL2; D007375:Interleukin-1; D016328:NF-kappa B; D016877:Oxidants; D012333:RNA, Messenger; D013439:Sulfhydryl Reagents; D003958:Diamide; D006861:Hydrogen Peroxide