Effects of phorbol ester on expression of CNTF-mRNA in cultured astrocytes from rat olfactory bulb

Ciliary neurotrophic factor (CNTF) is a neuropoietic cytokine which has various functions, such as survival promoting effect on both peripheral and central neurons, promotion of cholinergic differentiation, and participation in differentiation of Type-2 astrocytes (reviewed in ref. [30]). However, the regulatory mechanism of the CNTF expression is largely unknown. In this study, we analyzed the effects of phorbol 12-myristate 13-acetate (PMA), an activator of PKC, on the expression of CNTF-mRNA in cultured astrocytes from neonatal rat olfactory bulb. PMA induced a transient decrease of CNTF-mRNA levels which was followed by a persistent increase of the mRNA up to 4-fold of the control level at 24 h after the addition of the compound. Both the PMA-induced decrease and increase of the CNTF-mRNA levels were canceled by treatment with cycloheximide, an inhibitor of protein synthesis, suggesting that protein synthesis-dependent mechanisms participate in both the PMA-induced decrease and increase of CNTF-mRNA levels. On the other hand, PMA induced expressions of mRNAs of several subunit members of the AP-1 complex, such as c fos, c- jun and jun-B. Furthermore, dexamethasone, a synthetic glucocorticoid which is known to inhibit the AP-l complex-mediated transcription [14,27,36], canceled the PMA-induced decrease of the CNTF-mRNA levels. These results suggested that the AP-1 complex participates in the regulatory mechanism of the CNTF expression in the cultured astrocytes treated with PMA.