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-1 beta (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.
Pshenichkin
S P
SP
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
Wise
B C
BC
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D019319:Okadaic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases