HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print December 14, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0505252v1 81/3/835    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blanchette, J. Articles by Olivier, M. Search for Related Content PubMed PubMed Citation Articles by Blanchette, J. Articles by Olivier, M.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0505252

Received for publication May 9, 2005.
Revised November 14, 2006.
Accepted for publication November 17, 2006.

Article

Role of protein tyrosine phosphatases in the regulation of interferon--induced macrophage nitric oxide generation: implication of ERK pathway and AP-1 activation

Julie Blanchette ^*, Philippe Pouliot , and Martin Olivier ^*@

*Centre de Recherche en Infectiologie and Département de Biologie Médicale, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Université Laval, Ste-Foy, Québec, Canada; and Centre for the Study of Host Resistance, The Research Institute of the McGill University Health Centre, Departments of Experimental Medicine, Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada

^@ To whom correspondence should be addressed. E-mail: martin.olivier{at}mcgill.ca.

	Abstract

NO is a potent molecule involved in the cytotoxic events mediated by macrophages (M) against microorganisms. We reported previously that inhibition of M protein tyrosine phosphatases (PTPs) mediates a protective effect against Leishmania infection, which was NO-dependent. Herein, we show that the PTP inhibitors of the peroxovanadium (pV) class, bpV(phen) and bpV(pic), can similarly increase murine M IFN--induced NO generation. Using various second messenger (JAK2, MEK, Erk1/Erk2, and p38) antagonists, we found that the Erk1/Erk2 pathway was the principal pathway submitted to regulation by PTPs in the context of IFN--driven M activation and increase in NO production. We observed that bpV(phen) increases inducible NO synthase (iNOS) expression, resulting in enhanced NO production, whereas the bpV(pic) increase of NO production does not seem to result from a modulation of iNOS expression. Transcription factors STAT-1 and NF-B, recognized for their importance in NO generation, were not affected by the pV treatment. However, AP-1 was strongly activated by bpV(phen) but not by bpV(pic). Collectively, our results suggest that increased IFN--induced NO production, observed after bpV(phen) treatment, involves the activation of the transcription factor AP-1 by Erk1/Erk2- and stress-activated protein kinase/JNK-dependent transduction mechanisms.

Key Words: protein tyrosine kinases • transcription factors • peroxovanadiums • second messengers

This article has been cited by other articles:

				N. Rodriguez, R. Lang, N. Wantia, C. Cirl, T. Ertl, S. Durr, H. Wagner, and T. Miethke Induction of iNOS by Chlamydophila pneumoniae requires MyD88-dependent activation of JNK J. Leukoc. Biol., December 1, 2008; 84(6): 1585 - 1593. [Abstract] [Full Text] [PDF]

				S. Nakashima, S. A. Arnold, E. T. Mahoney, S. D. Sithu, Y. P. Zhang, S. E. D'Souza, C. B. Shields, and T. Hagg Small-Molecule Protein Tyrosine Phosphatase Inhibition as a Neuroprotective Treatment after Spinal Cord Injury in Adult Rats J. Neurosci., July 16, 2008; 28(29): 7293 - 7303. [Abstract] [Full Text] [PDF]