OKADAIC ACID STIMULATES NERVE GROWTH FACTOR PRODUCTION VIA AN INDUCTION OF INTERLEUKIN-1 IN PRIMARY CULTURES OF CORTICAL ASTROGLIAL CELLS

Neonatal rat cortical astroglial cells in primary culture synthesize and secrete interleukin-1β (IL-1) and nerve growth factor (NGF). Treatment of astrocytes with okadaic acid (OA), an inhibitor of phosphoprotein phosphatases, dramatically increased both IL-1 and NGF mRNA content (about 50-fold) with maximal induction seen at 20–30 nM OA. The induction of IL-1 mRNA preceded that of NGF mRNA and was maximal after 9 h of treatment. OA increased IL-1 mRNA half-life by about 10-fold similar to the reported stabilization of the NGF mRNA. Addition of an IL-1 receptor antagonist dose-dependently inhibited the secretion of NGF stimulated by OA and IL-1. The results indicate that OA profoundly stimulates IL-1 expression in glial cells by enhancing IL-1 mRNA stability and that glial cell-derived IL-1 acts in a paracrine/autocrine manner to stimulate NGF production. © 1997 Elsevier Science Ltd. All rights reserved