Polyunsaturated fatty acids and bovine interferon-tau modify phorbol ester-induced secretion of prostaglandin F2 alpha and expression of prostaglandin endoperoxide synthase-2 and phospholipase-A2 in bovine endometrial cells.
Embryonic mortality in cattle may occur because of inadequate inhibition of uterine secretion of prostaglandin (PG) F2alpha mediated by bovine interferon-tau (bIFN-tau). The objectives of the present study were to determine whether polyunsaturated fatty acids inhibit secretion of PGF2alpha from bovine endometrial cells induced by stimulating protein kinase C with phorbol 12,13 dibutyrate (PDBu) and to investigate possible mechanisms of action. Confluent cells were exposed for 24 h to 100 microM of linoleic, arachidonic (AA; C20:4, n-6), linolenic (LNA; C18:3, n-3), eicosapentaenoic (EPA; C20:5, n-3), or docosahexaenoic (DHA; C22:6, n-3) acid. After incubation, cells were washed and stimulated with PDBu. The EPA, DHA, and LNA attenuated secretion of PGF2alpha in response to PDBu. The EPA and DHA were more potent inhibitors than LNA. The EPA inhibited secretion of PGF2alpha at 6.25 microM. Secretion of PGF2alpha in response to PDBu decreased with increasing incubation time with EPA. Both bIFN-tau and EPA inhibited secretion of PGF2alpha, and their inhibitory effects were additive. The bIFN-tau, but not EPA, reduced the abundance of PG endoperoxide synthase-2 (PGHS-2) mRNA. Incubation with 100 microM EPA, DHA, or AA for 24 h followed by treatment with PDBu did not affect concentrations of PGHS-2 and phospholipase A2 proteins. The EPA and DHA inhibit secretion of PGF2alpha through a mechanism different from that of bIFN-tau. The effect of EPA on PGF2alpha secretion may be caused by competition with AA for PGHS-2 activity or reduction of PGHS-2 activity. The use of EPA and DHA to inhibit uterine secretion of PGF2alpha and to improve embryonic survival in cattle warrants further investigation.
Department of Animal Sciences, University of Florida, Gainesville, Florida 32611-0910, USA.
Ricardo
R
Mattos
Aydin
A
Guzeloglu
Lokenga
L
Badinga
Charles R
CR
Staples
William W
WW
Thatcher
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D015152:Blotting, Northern; D002417:Cattle; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D019787:Linoleic Acid / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000502:physiology; D011257:Pregnancy Proteins / Q000502:physiology*; D011270:Pregnancy, Animal / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis
D020536:Enzyme Activators; D005231:Fatty Acids, Unsaturated; D007370:Interferon Type I; D007527:Isoenzymes; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C020947:interferon tau; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; D015237:Dinoprost; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2