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, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

PGs are potent mediators of pain and inflammation. PGE synthases (PGES) catalyze the isomerization of PGH 2 into PGE 2. The microsomal (m)PGES-1 isoform serves as an inducible PGES and is responsible for the production of PGE 2, 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-γ 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 PGE 2 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.

Original languageEnglish
Pages (from-to)320-326
Number of pages7
JournalJournal of Leukocyte Biology
Volume82
Issue number2
DOIs
Publication statusPublished - Aug 1 2007

Keywords

  • COX-2
  • Cytokines
  • Inflammation
  • PGE2

ASJC Scopus subject areas

  • Cell Biology

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