Dual specificity phosphatase 1 regulates human inducible nitric oxide synthase expression by p38 MAP kinase

Research output: Contribution to journalArticle

Authors

  • Riku Korhonen
  • Tuija Turpeinen
  • Riina Nieminen
  • Ville Taimi
  • Taina Heittola
  • Outi Sareila
  • Eeva Moilanen

Colleges, School and Institutes

External organisations

  • University of Tampere School
  • Imperial College London

Abstract

The role of dual specificity phosphatase 1 (DUSP1) in inducible nitric oxide synthase (iNOS) expression in A549 human pulmonary epithelial cells, J774 mouse macrophages and primary mouse bone marrow-derived macrophages (BMMs) was investigated. iNOS expression was induced by a cytokine mixture (TNF, IFN and IL-1) in A549 cells and by LPS in J774 cells, and it was inhibited by p38 MAPK inhibitors SB202190 and BIRB 796. Stimulation with cytokine mixture or LPS enhanced also DUSP1 expression. Down-regulation of DUSP1 by siRNA increased p38 MAPK phosphorylation and iNOS expression in A549 and J774 cells. In addition, LPS-induced iNOS expression was enhanced in BMMs from DUSP1((-/-)) mice as compared to that in BMMs from wild-type mice. The results indicate that DUSP1 suppresses iNOS expression by limiting p38 MAPK activity in human and mouse cells. Compounds that enhance DUSP1 expression or modulate its function may be beneficial in diseases complicated with increased iNOS-mediated NO production.

Details

Original languageEnglish
Article number127587
JournalMediators of Inflammation
Volume2011
Publication statusPublished - 22 Jun 2011

ASJC Scopus subject areas