Regulation of Prostaglandin Endoperoxide Synthase-2 and IL-6 Expression in Mouse Bone Marrow-Derived Mast Cells by Exogenous But Not Endogenous Prostanoids

• Published in: The Journal of immunology (1950) 2002-02, Vol.168 (3), p.1397-1404
• Main Authors: Diaz, Bruno L, Fujishima, Hiroshi, Kanaoka, Yoshihide, Urade, Yoshihiro, Arm, Jonathan P
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Bone Marrow Cells - drug effects; Bone Marrow Cells - enzymology; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Cells, Cultured; Cyclooxygenase 2; Cytokines - physiology; Dinoprostone - pharmacology; Interleukin-6 - biosynthesis; Interleukin-6 - metabolism; Isoenzymes - biosynthesis; Male; Mast Cells - drug effects; Mast Cells - enzymology; Mast Cells - immunology; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; Nitrobenzenes - pharmacology; peroxisome proliferator-activated receptor-^g; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Prostaglandin endoperoxide synthase 2; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandins - pharmacology; Prostaglandins - physiology; Sulfonamides - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.3.1397

Mouse bone marrow-derived mast cells (BMMC), stimulated with stem cell factor, IL-1beta, and IL-10, secrete IL-6 and demonstrate a delayed phase of PGD(2) generation that is dependent upon the induced expression of PG endoperoxide synthase (PGHS)-2. We have examined the potential for exogenous prostanoids, acting in a paracrine fashion, and endogenous prostanoids, acting in an autocrine fashion, to regulate PGHS-2 induction and IL-6 secretion in mouse BMMC. Exogenous PGE(2), which acts through G protein-coupled receptors, and 15-deoxy-Delta(12,14)-PGJ(2), which is a ligand for peroxisome proliferator-activated receptor (PPAR)gamma, elicited a 2- to 3-fold amplification of PGHS-2 induction, delayed-phase PGD(2) generation, and IL-6 secretion in response to stem cell factor, IL-1beta, and IL-10. The effect of PGE(2) was reproduced by the E prostanoid (EP)1 receptor agonist 17-trinor-PGE(2), and the EP1/EP3 agonist, sulprostone, but not the EP2 receptor agonist, butaprost. Although BMMC express PPARgamma, the effects of 15-deoxy-Delta(12,14)-PGJ(2) were not reproduced by the PPARgamma agonists, troglitazone and ciglitazone. PGHS-2 induction, but not IL-6 secretion, was impaired in cPLA(2)-deficient BMMC. However, there was no impairment of PGHS-2 induction in BMMC deficient in hematopoietic PGD synthase or PGHS-1 in the presence or absence of the PGHS-2 inhibitor, NS-398. Thus, although exogenous prostanoids may contribute to amplification of the inflammatory response by augmenting PGD(2) generation and IL-6 secretion from mast cells, endogenous prostanoids do not play a role.