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

Cytokine. 1997 Mar;9(3):178-86. doi: 10.1006/cyto.1996.0152.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / pharmacology
  • Binding Sites
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Diamide / pharmacology
  • Gene Expression Regulation / drug effects*
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Interleukin-1 / pharmacology*
  • NF-kappa B / metabolism*
  • Oxidants / pharmacology
  • Oxidation-Reduction
  • RNA, Messenger / metabolism
  • Sulfhydryl Reagents / pharmacology

Substances

  • Antioxidants
  • Chemokine CCL2
  • Interleukin-1
  • NF-kappa B
  • Oxidants
  • RNA, Messenger
  • Sulfhydryl Reagents
  • Diamide
  • Hydrogen Peroxide