PROTEIN-KINASES AND PROSTAGLANDIN PRODUCTION IN OVINE ASTROGLIA

We examined 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 F-2 alpha (PGF(2 alpha)) levels were analyzed using enzyme immunoassay. Application of IL-1 alpha augmented the production 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), blocked IL-1 alpha-induced PGF(2 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 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 alpha 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 astroglia via steps involving activation of PKC and increased activity of COX and PLA(2).