TY - JOUR
T1 - Regulation of the microsomal prostaglandin E synthase-1 in polarized mononuclear phagocytes and its constitutive expression in neutrophils
AU - Mosca, Michela
AU - Polentarutti, Nadia
AU - Mangano, Giorgina
AU - Apicella, Claudia
AU - Doni, Andrea
AU - Mancini, Francesca
AU - De Bortoli, Maida
AU - Coletta, Isabella
AU - Polenzani, Lorenzo
AU - Santoni, Giorgio
AU - Sironi, Marina
AU - Vecchi, Annunciata
AU - Mantovani, Alberto
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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.
AB - 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.
KW - COX-2
KW - Cytokines
KW - Inflammation
KW - PGE2
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U2 - 10.1189/jlb.0906576
DO - 10.1189/jlb.0906576
M3 - Article
C2 - 17505022
AN - SCOPUS:34547746024
VL - 82
SP - 320
EP - 326
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 2
ER -