Activation of nuclear factor-kappa B correlates with MCP-1 expression by human mesangial cells

Kidney Int. 1995 Oct;48(4):1263-71. doi: 10.1038/ki.1995.410.


Emerging evidence suggests that mesangial cell-derived monocyte chemoattractant protein-1 (MCP-1) is a potentially important mediator of glomerular monocyte infiltration. Interleukin-1 beta (IL-1) has been found in glomeruli during inflammation, and is a potent inducer of MCP-1 expression by mesangial cells. Analysis of the promoter region of the human MCP-1 gene demonstrates several putative binding sites for transcription activating factors, including recognition elements for the IL-1-inducible transcription factor, nuclear factor-kappa B (NF-kappa B). This study investigated the role of NF-kappa B in IL-1-induced MCP-1 expression by human mesangial cells. We found that treating mesangial cells with IL-1 resulted in the rapid activation (within 30 min) and nuclear translocation of NF-kappa B. NF-kappa B activation could be blocked by preventing the proteolytic degradation of I kappa B, the cytoplasmic inhibitor of NF-kappa B, with the protease inhibitor tosyl-phe-chloromethylketone (TPCK). Inhibition of NF-kappa B with TPCK correlated with a dose-dependent reduction in IL-1-induced MCP-1 mRNA levels. Conversely, raising intracellular cyclic-AMP levels, or exposing mesangial cells to herbimycin A, treatments that block IL-1-induced MCP-1 mRNA expression, significantly attenuated NF-kappa B activation. Finally, blocking the synthesis of one of the protein subunits of NF-kappa B with an antisense oligonucleotide decreased MCP-1 mRNA levels in response to IL-1. These data suggest that MCP-1 gene transcription may be mediated, in part, by the transcription factor NF-kappa B.

Publication types

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

MeSH terms

  • Antioxidants / pharmacology
  • Base Sequence
  • Cells, Cultured
  • Chemokine CCL2 / genetics*
  • Gene Expression / drug effects
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Humans
  • Interleukin-1 / pharmacology
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Serine Proteinase Inhibitors / pharmacology
  • Thiocarbamates / pharmacology
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology


  • Antioxidants
  • Chemokine CCL2
  • Interleukin-1
  • NF-kappa B
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Serine Proteinase Inhibitors
  • Thiocarbamates
  • prolinedithiocarbamate
  • Tosylphenylalanyl Chloromethyl Ketone
  • Proline