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

Published online before print May 15, 2007

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0906576v1 82/2/320    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 Mosca, M. Articles by Mantovani, A. Search for Related Content PubMed PubMed Citation Articles by Mosca, M. Articles by Mantovani, A.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0906576

Received for publication September 19, 2006.
Revised April 4, 2007.
Accepted for publication April 12, 2007.

Article

Regulation of the microsomal prostaglandin E synthase-1 in polarized mononuclear phagocytes and its constitutive expression in neutrophils

Michela Mosca ^*, Nadia Polentarutti , Giorgina Mangano , Claudia Apicella , Andrea Doni , Francesca Mancini , Maida De Bortoli ^*, Isabella Coletta , Lorenzo Polenzani , Giorgio Santoni , Marina Sironi , Annunciata Vecchi ^@, and Alberto Mantovani ^||

*Department of Immunology and Cell Biology, Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy; Istituto Clinico Humanitas, Rozzano, Italy; Angelini Farmaceutici-A.C.R.A.F., Piazzale della Stazione, Rome, Italy; Department of Experimental Medicine and Public Health, Università of Camerino, Italy; and ^||Institute of General Pathology, Medical Faculty, University of Milan, Italy

^@ To whom correspondence should be addressed. E-mail: annunciata.vecchi{at}humanitas.it.

	Abstract

PGs are potent mediators of pain and inflammation. PGE synthases (PGES) catalyze the isomerization of PGH₂ into PGE₂. The microsomal (m)PGES-1 isoform serves as an inducible PGES and is responsible for the production of PGE₂, which mediates acute pain in inflammation and fever. The present study was designed to investigate the regulation of expression of mPGES-1 in polarized phagocytes, which represent central, cellular orchestrators of inflammatory reactions. Here, we report that human peripheral blood monocytes did not express mPGES-1. Exposure to LPS strongly induced mPGES-1 expression. Alternatively activated M2 monocytes-macrophages exposed to IL-4, IL-13, or IL-10 did not express mPGES-1, whereas in these cells, IL-4, IL-13, and to a lesser extent, IL-10 or IFN- inhibited LPS-induced, mPGES-1 expression. It is unexpected that polymorphonuclear leukocytes expressed high basal levels of mPGES-1, which was up-regulated by LPS and down-regulated by IL-4 and IL-13. Induction of mPGES-1 and its modulation by cytokines were confirmed at the protein level and correlated with PGE₂ production. Cyclooxygenase 2 expression tested in the same experimental conditions was modulated in monocytes and granulocytes similarly to mPGES-1. Thus, activated M1, unlike alternatively activated M2, mononuclear phagocytes express mPGES-1, and IL-4, IL-13, and IL-10 tune expression of this key enzyme in prostanoid metabolism. Neutrophils, the first cells to enter sites of inflammation, represent a ready-made, cellular source of mPGES-1.

Key Words: cytokines • PGE2 • COX-2 • inflammation

This article has been cited by other articles:

				N. Degousee, S. Fazel, D. Angoulvant, E. Stefanski, S.-C. Pawelzik, M. Korotkova, S. Arab, P. Liu, T. F. Lindsay, S. Zhuo, et al. Microsomal Prostaglandin E2 Synthase-1 Deletion Leads to Adverse Left Ventricular Remodeling After Myocardial Infarction Circulation, April 1, 2008; 117(13): 1701 - 1710. [Abstract] [Full Text] [PDF]