Transcriptional and Posttranscriptional Mechanisms Involved in the Interleukin-1, Steroid, and Protein Kinase C Regulation of Nerve Growth Factor in Cortical Astrocytes
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 2, pages 419–428, August 1994
How to Cite
Pshenichkin, S. P., Szekely, A. M. and Wise, B. C. (1994), Transcriptional and Posttranscriptional Mechanisms Involved in the Interleukin-1, Steroid, and Protein Kinase C Regulation of Nerve Growth Factor in Cortical Astrocytes. Journal of Neurochemistry, 63: 419–428. doi: 10.1046/j.1471-4159.1994.63020419.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received August 24, 1993; revised manuscript received December 2, 1993; accepted December 13, 1993.
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Abstract: Neonatal rat cortical astrocytes in primary culture synthesize and secrete nerve growth factor (NGF). Treatment of astrocytes with interleukin-1β (IL-1) or the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA) increased NGF mRNA content by six- to 10-fold, followed in time by increases in cell content and cell secretion of NGF. Dexamethasone potently inhibited the effects of IL-1 and TPA on astroglial cell NGF expression. The action of IL-1 was not mediated by PKC because treatment of cells with maximal concentrations of both IL-1 and TPA gave an additive increase in NGF mRNA content and NGF secretion, and because down-regulating PKC activity failed to inhibit the stimulatory effects of IL-1. Moreover, both agents increased NGF gene transcription in nuclear run-on assays, but only IL-1 significantly stabilized the NGF mRNA. An analysis of the effects of IL-1 and TPA on immediate early gene expression indicated that IL-1 preferentially induced c-jun gene expression, whereas TPA greatly increased c-fos and zif/268 gene expression. These results suggest that IL-1 activates c-jun and NGF gene expression, and NGF mRNA stabilization in astrocytes by a distinct PKC-independent signaling pathway.