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

Yuhko Shibuya, Noriyasu Hirasawa, Takumi Sakai, Yuhko Togashi, Rieko Muramatsu, Ken Ichi Ishii, Masamichi Yamashita, Motoaki Takayanagi, Kazuo Ohuchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

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-γ (IFN-γ) (100 U/ml) induced phosphorylation of p44/42 MAPK. The MEK inhibitor U0126 (0.1 to 10 μM) enhanced the TPA-induced ICAM-1 expression but not the IFN-γ-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 μM), 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 κB (NF-κB) activation, and MG132, a 26S proteasome inhibitor, reduced the TPA-induced ICAM-1 expression but not the IFN-γ-induced one. TPA partially decreased the level of IκB-α 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-κB activation, thus negatively regulating the PKC activator-induced ICAM-1 expression but not the IFN-γ-induced one.

Original languageEnglish
Pages (from-to)435-446
Number of pages12
JournalLife Sciences
Volume75
Issue number4
DOIs
Publication statusPublished - 2004 Jun 11

Keywords

  • Epithelial cells
  • Intercellular adhesion molecule-1
  • Interferon-γ
  • Nuclear factor-κB (NF-κB)
  • Protein kinase C
  • p44/42 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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