Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates nitric oxide-induced activator protein-1 activation in human bronchial epithelial cells

Itsuro Jibiki, Shu Hashimoto, Shuichiro Maruoka, Yasuhiro Gon, Atsushi Matsuzawa, Hideki Nishitoh, Hidenori Ichijo, Takashi Horie

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Exhaled nitric oxide (NO) is increased in individuals with bronchial asthma. NO may have antiinflammatory and proinflammatory effects; however, its role in bronchial asthma is unclear. In the present study, to clarify this issue we examined the effect of NO in inducing activator protein-1 (AP-1) activation in human bronchial epithelial cells (BEC) and a role of apoptosis signal-regulating kinase1 (ASK1), an upstream kinase kinase of c-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in NO-mediated AP-1 activation. The results showed that (1) the reactive nitrogen generating species NOR-1(±-(E)-methyl-2-[(E)-hydroxykmino]-5-nitro-6-methoxy-3- hexeneamide]) induced AP-1 activation determined by AP-1-dependent luciferase gene activity, and an NO scavenger, carboxyl-PTIO, attenuated NOR-1-induced AP-1 activation; (2) NOR-1 phosphorylated ASK1, JNK, and p38 MAPK; and (3) transient transfection of the dominant negative form of AKS1 attenuated NOR-1-induced AP-1 activation in BEC. To further characterize the role of ASK-1 cascade, the dominant negative form of ASK1-stable transfected porcine artery endothelial (PAE) cells were used. AP-1 activity and JNK and p38 MAPK phosphorylation were depressed in the dominant-negative form of ASK1-stable transfected PAE cells. These results indicate that NO is capable of inducing AP-1 activation, and that ASK1-p38 MAPK/JNK cascade regulates AP-1 activation in NO-stimulated BEC.

Original languageEnglish
Pages (from-to)856-861
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume167
Issue number6
DOIs
Publication statusPublished - 2003 Mar 15
Externally publishedYes

Keywords

  • Activator protein-1
  • Airway inflammation
  • Bronchial epithelium
  • Mitogen-activated protein kinase
  • Nitric oxide

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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