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Regulation of the microsomal prostaglandin E synthase‐1 in polarized mononuclear phagocytes and its constitutive expression in neutrophils
Author(s) -
Mosca Michela,
Polentarutti Nadia,
Mangano Giorgina,
Apicella Claudia,
Doni Andrea,
Mancini Francesca,
De Bortoli Maida,
Coletta Isabella,
Polenzani Lorenzo,
Santoni Giorgio,
Sironi Marina,
Vecchi Annunciata,
Mantovani Alberto
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0906576
Subject(s) - inflammation , biology , eicosanoid , cyclooxygenase , prostaglandin e , chemotaxis , peripheral blood mononuclear cell , microbiology and biotechnology , immunology , enzyme , biochemistry , in vitro , receptor , arachidonic acid
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.