title: Protein kinases and prostaglandin production in ovine astroglia.
abstract: We examined the effects of interleukin-1 alpha (IL-1 alpha) and involvement of protein kinases on prostaglandin production in cultured ovine astroglia. Ovine astroglia were exposed to media alone, or 10 ng/mL IL-1 alpha and prostaglandin F2 alpha (PGF2 alpha) levels were analyzed using enzyme immunoassay. Application of IL-1 alpha augmented the production of PGF2 alpha at 4 h. Coapplication of H-7 (10-1000 microM) and staurosporine (0.1-10 microM), inhibitors of protein kinase C (PKC), blocked IL-1 alpha-induced PGF2 alpha production. IL-1 alpha increased cyclooxygenase (COX) activity while coapplication of staurosporine prevented an increase, implying that COX activity was dependent upon PKC activation. In contrast, forskolin, sodium nitroprusside, and cyclic nucleotide analogs alone did not affect prostaglandin production significantly, excluding the involvement of cAMP/cGMP-dependent protein kinases. Coapplication of quinacrine (10 microM) and bromophenacyl bromide (100 microM), inhibitors of phospholipase A2 (PLA2), prevented the IL-1 alpha-induced increases in PGF2 alpha production. Lastly, IL-1 alpha increased labeled arachidonic acid (AA) release whereas coaddition of quinacrine (10 microM) attenuated increased AA release. Therefore, we propose that IL-1 alpha enhances prostaglandin production by ovine astroglia via steps involving activation of PKC and increased activity of COX and PLA2.
authors.affiliation: Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1083, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Nam
authors.forename: C
authors.initials: C
authors.lastname: Thore
authors.forename: D
authors.initials: D
authors.lastname: Busija
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015237:Dinoprost / Q000032:analysis / Q000096:biosynthesis; D004789:Enzyme Activation; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011454:Prostaglandins A / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D012756:Sheep
chemical_list: D007375:Interleukin-1; D011453:Prostaglandins; D011454:Prostaglandins A; D017472:Receptors, Interleukin-1; D016718:Arachidonic Acid; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; C100008:prostaglandin A2