Effect of calcitriol in combination with corticosterone, interleukin-1beta, and transforming growth factor-beta1 on nerve growth factor secretion in an astroglial cell line.
In astrocytes, nerve growth factor (NGF) synthesis has been described to be stimulated by the cytokines interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) and inhibited by corticosterone. As all three factors are present in the brain under certain conditions, we investigated the effect of their combined application on NGF secretion in the astroglial cell line RC7 and, in addition, studied the effect of calcitriol (1alpha,25-dihydroxyvitamin D3). Calcitriol stimulated NGF secretion, whereas corticosterone reduced basal levels of NGF secretion as well as inhibited the NGF secretion induced by IL-1beta, calcitriol, and TGF-beta1. Calcitriol had an additive effect when applied together with IL-1beta and a synergistic effect when applied with TGF-beta1. Moreover, calcitriol not only counteracted the inhibitory effect of corticosterone on NGF secretion stimulated by TGF-beta1 but even augmented it to a level more than threefold higher than that reached with TGF-beta1 alone. Due to the trophic effect of NGF on basal forebrain cholinergic neurons, these findings might be of therapeutic relevance under conditions where cholinergic function is impaired and the endogenous levels of corticosterone, IL-1beta, or TGF-beta1 are elevated.
Hahn
M
M
Preclinical Research, PRPN, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Lorez
H
H
Fischer
G
G
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002531:Cerebellum / Q000166:cytology; D003345:Corticosterone / Q000494:pharmacology*; D004347:Drug Interactions; D007375:Interleukin-1 / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D009414:Nerve Growth Factors; D016212:Transforming Growth Factor beta; D002117:Calcitriol; D003345:Corticosterone