Regulation of prostaglandin endoperoxide synthase-2 and IL-6 expression in mouse bone marrow-derived mast cells by exogenous but not endogenous prostanoids.
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.
Diaz
Bruno L
BL
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Fujishima
Hiroshi
H
Kanaoka
Yoshihide
Y
Urade
Yoshihiro
Y
Arm
Jonathan P
JP
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009578:Nitrobenzenes / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011453:Prostaglandins / Q000494:pharmacology* / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D015850:Interleukin-6; D007527:Isoenzymes; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2