Lysophosphatidic acid stimulates prostaglandin E2 production in cultured stromal endometrial cells through LPA1 receptor.
Lysophosphatidic acid (LPA) has been shown to be a potent modulator of prostaglandin (PG) secretion during the luteal phase of the estrous cycle in the bovine endometrium in vivo. The aims of the present study were to determine the cell types of the bovine endometrium (epithelial or stromal cells) responsible for the secretion of PGs in response to LPA, the cellular, receptor, intracellular, and enzymatic mechanisms of LPA action. Cultured bovine epithelial and stromal cells were exposed to LPA (10(-5)-10(-9) M), tumor necrosis factor alpha (TNFalpha; 10 ng/mL) or oxytocin (OT; 10(-7) M) for 24 h. LPA treatment resulted in a dose-dependent increase of PGE(2) production in stromal cells, but not in epithelial cells. LPA did not influence PGF(2alpha) production in stromal or epithelial cells. To examine which type of LPA G-protein-coupled receptor (LP-GPCR; LPA1, LPA2, or LPA3) is responsible for LPA action, stromal cells were preincubated with three selected blockers of LPA receptors: NAEPA, DGPP, and Ki16425 for 0.5 h, and then stimulated with LPA. Only Ki16425 inhibited the stimulatory effect of LPA on PGE(2) production and cell proliferation in the stromal cells. LPA-induced intracellular calcium ion mobilization was also inhibited only by Ki16425. Finally, we examined whether LPA-induced PGE(2) synthesis in stromal cells is via the influence on mRNA expression for the enzymes responsible for PGE(2) synthesis-PGE(2) synthase (PGES) and PG-endoperoxide synthase 2 (PTGS2). We demonstrated that the stimulatory effect of LPA on PGE(2) production in stromal cells is via the stimulation of PTGS2 and PGES mRNA expression in the cells. The overall results indicate that LPA stimulates PGE(2) production, cell viability, and intracellular calcium ion mobilization in cultured stromal endometrial cells via Ki16425-sensitive LPA1 receptors. Moreover, LPA exerts a stimulatory effect on PGE(2) production in stromal cells via the induction of PTGS2 and PGES mRNA expression.
Woclawek-Potocka
Izabela
I
Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland. wiza@pan.olsztyn.pl
Kondraciuk
Katarzyna
K
Skarzynski
Dariusz Jan
DJ
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D011756:Diphosphates / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*
C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D011756:Diphosphates; D007555:Isoxazoles; D008246:Lysophospholipids; D011422:Propionates; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; C408642:diacylglycerol pyrophosphate; D015237:Dinoprost; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D005990:Glycerol; C032881:lysophosphatidic acid