Negative regulation of the protein kinase C activator-induced ICAM-1 expression in the human bronchial epithelial cell line NCI-H292 by p44/42 mitogen-activated protein kinase

Life Sci. 2004 Jun 11;75(4):435-46. doi: 10.1016/j.lfs.2003.12.016.

Abstract

The role of p44/42 mitogen-activated protein kinase (MAPK) in the expression of intercellular adhesion molecule-1 (ICAM-1) in NCI-H292 cells, a human bronchial epithelial cell line, was analyzed. Treatment with the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) or interferon-gamma (IFN-gamma) (100 U/ml) induced phosphorylation of p44/42 MAPK. The MEK inhibitor U0126 (0.1 to 10 microM) enhanced the TPA-induced ICAM-1 expression but not the IFN-gamma-induced one. U0126 also enhanced the ICAM-1 expression induced by two other PKC activators teleocidin (22.5 nM) and aplysiatoxin (14.9 nM). Furthermore, PD98059 (0.5 to 50 microM), another MEK inhibitor, enhanced the TPA-induced ICAM-1 expression as well. The inhibitor of p38 MAPK SB203580 did not affect the TPA-induced ICAM-1 expression. BAY11-7082, an inhibitor of nuclear factor kappaB (NF-kappaB) activation, and MG132, a 26S proteasome inhibitor, reduced the TPA-induced ICAM-1 expression but not the IFN-gamma-induced one. TPA partially decreased the level of IkappaB-alpha and the reduction was further augmented by U0126 in a concentration-dependent manner. These findings suggested that, in NCI-H292 cells, p44/42 MAPK suppresses PKC activator-induced NF-kappaB activation, thus negatively regulating the PKC activator-induced ICAM-1 expression but not the IFN-gamma-induced one.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Bronchi / cytology
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / enzymology
  • Epithelial Cells* / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Interferon-gamma / pharmacology
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Enzyme Inhibitors
  • NF-kappa B
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase Kinases
  • MAP3K1 protein, human
  • Tetradecanoylphorbol Acetate