PROTEIN-KINASES AND PROSTAGLANDIN PRODUCTION IN OVINE ASTROGLIA

We examined effects of interleukin-1 alpha (IL-1 alpha) and involvemen t of protein kinases on prostaglandin production in cultured ovine ast roglia. Ovine astroglia were exposed to media alone, or 10 ng/mL IL-1 alpha and prostaglandin F-2 alpha (PGF(2 alpha)) levels were analyzed using enzyme immunoassay. Application of IL-1 alpha augmented the prod uction of PGF(2 alpha) at 4 h. Coapplication of H-7 (10-1000 mu M) and staurosporine (0.1-10 mu M), inhibitors of protein kinase C (PKC), bl ocked IL-1 alpha-induced PGF(2 alpha) production. IL-1 alpha increased cyclooxygenase (COX) activity while coapplication of staurosporine pr evented 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 signi ficantly excluding the involvement of cAMP/cGMP-dependent protein kina ses. Coapplication of quinacrine (10 mu M) and bromophenacyl bromide ( 200 mu M), inhibitors of phospholipase A(2) (PLA(2)), prevented the IL -1 alpha-induced increases in PGF(2 alpha) production. Lastly IL-1 alp ha increased labeled arachidonic acid (AA) release whereas coaddition of quinacrine (10 mu M) attenuated increased AA release. Therefore, we propose that IL-1 alpha enhances prostaglandin production by ovine as troglia via steps involving activation of PKC and increased activity o f COX and PLA(2).