The mitogen-activated protein kinase p38 is necesssary for interleukin 1beta-induced monocyte chemoattractant protein 1 expression by human mesangial cells

Cytokine. 1999 Feb;11(2):118-26. doi: 10.1006/cyto.1998.0409.

Abstract

Mitogen-activated protein (MAP) kinases have been suggested as potential mediators for interleukin 1beta (IL-1beta)-induced gene activation. This study investigated the role of the MAP kinases p38 and ERK2 in IL-1beta-mediated expression of the chemokine MCP-1 by human mesangial cells. Phosphorylation of p38 kinase, which is necessary for activation, increased significantly after IL-1beta treatment. p38 kinase immunoprecipitated from IL-1beta-treated cells phosphorylated target substrates to a greater extent than p38 kinase from controls. SB 203580, a selective p38 kinase inhibitor, was used to examine the role of p38 kinase in MCP-1 expression. SB 203580 decreased IL-1beta-induced MCP-1 mRNA and protein levels, but did not affect MCP-1 mRNA stability. Because NF-kappaB is necessary for MCP-1 gene expression, the effect of p38 kinase inhibition on IL-1beta induction of NF-kappaB was measured. SB 203580 (up to 25 microM) had no effect on IL-1beta-induced NF-kappaB nuclear translocation or DNA binding activity. Our previous work showed that IL-1beta also activates the MAP kinase ERK2 in human mesangial cells. PD 098059, a selective inhibitor of the ERK activating kinase MEK1, had no effect on IL-1beta-induced MCP-1 mRNA or protein levels, or on IL-1beta activation of NF-kappaB. These data indicate that p38 kinase is necessary for the induction of MCP-1 expression by IL-1beta, but is not involved at the level of cytoplasmic activation of NF-kappaB. In contrast, ERK2 does not mediate IL-1beta induced MCP-1 gene expression.

Publication types

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

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology*
  • Cells, Cultured
  • Chemokine CCL2 / biosynthesis*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Gene Expression / drug effects
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-1 / pharmacology*
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases*
  • NF-kappa B / metabolism
  • Pyridines / pharmacology
  • RNA, Messenger / metabolism
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Chemokine CCL2
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Interleukin-1
  • NF-kappa B
  • Pyridines
  • RNA, Messenger
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one