Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2011, Article ID 127587, 15 pages
http://dx.doi.org/10.1155/2011/127587
Research Article

Dual Specificity Phosphatase 1 Regulates Human Inducible Nitric Oxide Synthase Expression by p38 MAP Kinase

1The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Medisiinarinkatu 3, 33014 Tampere, Finland
2The Kennedy Institute of Rheumatology, Imperial College London, London W6 8LH, UK

Received 17 December 2010; Accepted 15 February 2011

Academic Editor: Fulvio D'Acquisto

Copyright © 2011 Tuija Turpeinen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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, IFNγ and IL-1β) 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.