Prostaglandin E(2) receptors, EP2 and EP4, differentially modulate TNF-alpha and IL-6 production induced by lipopolysaccharide in mouse peritoneal neutrophils.

The expression and function of prostaglandin (PG) E(2) receptors were examined in mouse neutrophils exudated into the peritoneal cavity by casein treatment. Expressions of the EP2 and EP4 receptors were detected in neutrophils by Northern blot, but those of EP1 and EP3 receptors were not detected by RT-PCR. EP2-selective agonist, ONO-AE1-259, and EP4-selective agonist, ONO-AE1-329, stimulated cAMP formation in the cells. PGE(2) affected the TNF-alpha and IL-6 production in lipopolysaccharide (LPS)-treated neutrophils; it suppressed the TNF-alpha production and enhanced the IL-6 production. The PGE(2) effects were mimicked by dibutyryl cAMP. This is the first study of the enhancement of IL-6 production by cAMP-elevating reagents in neutrophils. Using neutrophils from EP2- and EP4-deficient mice in combination with EP2- and EP4-selective agonists, it was found that the augmentation of IL-6 was mediated mainly by the EP2 receptor and the suppression of TNF-alpha by the EP4 receptor and partially by the EP2 receptor. These findings indicate that casein-induced peritoneal neutrophils express Gs-coupled PGE(2) receptors, EP2 and EP4, which might differentially regulate the LPS-induced production of TNF-alpha and IL-6.

Yamane H ，Sugimoto Y ，Tanaka S ，Ichikawa A ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

E-prostanoid (EP)2/EP4 receptor-dependent maturation of human monocyte-derived dendritic cells and induction of helper T2 polarization.

Kubo S ，Takahashi HK ，Takei M ，Iwagaki H ，Yoshino T ，Tanaka N ，Mori S ，Nishibori M ... -  《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》

Prostaglandin E2 (PGE2) downregulates interleukin (IL)-1alpha-induced IL-6 production via EP2/EP4 subtypes of PGE2 receptors in human periodontal ligament cells.

Noguchi K ，Maeda M ，Ruwanpura SM ，Ishikawa I ... -  《ORAL DISEASES》

Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling.

Gray T ，Nettesheim P ，Loftin C ，Koo JS ，Bonner J ，Peddada S ，Langenbach R ... -  《MOLECULAR PHARMACOLOGY》

Exogenous but not endogenous prostanoids regulate cytokine secretion from murine bone marrow dendritic cells: EP2, DP, and IP but not EP1, EP3, and FP prostanoid receptors are involved.

Józefowski S ，Bobek M ，Marcinkiewicz J 《INTERNATIONAL IMMUNOPHARMACOLOGY》