Selective Induction of Prostaglandin G/H Synthase I by Stem Cell Factor and Dexamethasone in Mast Cells (∗)

• Published in: The Journal of biological chemistry Vol. 270; no. 14; pp. 8044 - 8049
• Main Authors: Samet, James M., Fasano, Mary Beth, Fonteh, Alfred N., Chilton, Floyd H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.04.1995; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Cells, Cultured; Cyclooxygenase Inhibitors - pharmacology; Dexamethasone - pharmacology; Enzyme Induction; Hematopoietic Cell Growth Factors - pharmacology; Interleukin-3 - pharmacology; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - enzymology; Mice; Mice, Inbred CBA; Phospholipases A - antagonists & inhibitors; Phospholipases A - biosynthesis; Phospholipases A2; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem Cell Factor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.14.8044

This study examines the regulatory effects of two cytokines, stem cell factor (SCF) and interleukin-3, and a glucocorticoid, dexamethasone, on lipid mediator generation in mouse bone marrow-derived mast cells (BMMC). Treatment of BMMC with SCF induced a modest, dose-dependent increase in three eicosanoids, thromboxane B2, prostaglandin D2, and leukotriene B4. These increases were accompanied by a marked elevation in cytosolic PLA2 (cPLA2). Dexamethasone blocked the induction of cPLA2 levels and the elevation in leukotriene B4 induced by SCF. By contrast, the combination of SCF and dexamethasone dramatically increased (5-8-fold) the capacity by BMMC to produce prostanoid products. This increase in prostanoid products was mirrored by an increase in prostaglandin G/H synthase I (PGHS-I) levels. Dexamethasone, alone, had no effect on PGHS-I, cPLA2, or prostanoid levels. Moreover, neither SCF or dexamethasone, alone or in combination, influenced prostaglandin G/H synthase II (PGHS-II) levels. In contrast to SCF, interleukin-3 alone or in combination with dexamethasone had no effect on prostanoid synthesis or PGHS-I or II levels. To better understand the SCF and dexamethasone effect, PGHS-I and PGHS-II mRNA expression were examined by Northern analysis. PGHS-I mRNA was markedly induced (maximal levels at 5 h) by the combination of SCF and dexamethasone. PGHS-II mRNA was undetectable in either control or SCF/dexamethasone-treated BMMC. Neither SCF or dexamethasone, alone, altered mRNA for either PGHS isotype. Taken together, these studies reveal that PGHS-I may be critical to prostanoid formation in mast cells exposed to cytokines and glucocorticoids. Moreover, they suggest that synergistic induction of PGHS-I could represent a novel mechanism for the anti-inflammatory action of glucocorticoids.