STAT PROTEINS ARE ACTIVATED BY CILIARY NEUROTROPHIC FACTOR IN CELLS OF CENTRAL-NERVOUS-SYSTEM ORIGIN

Neuropoietic cytokines, including ciliary neurotrophic factor (CNTF) a nd leukemia inhibitory factor (LIF), have survival effects on cells of the peripheral and central nervous systems (PNS and CNS), CNTF and LI F also produce differentiation in some cells of the PNS, We have shown previously that CNTF activates the signal transducers and activators of transcription (STAT) family of transcription factors, and that this signaling pathway may be one of several employed by CNTF to regulate the expression of the vasoactive intestinal peptide (VIP) gene in cell s of the PNS (Symes et al.: Proc Natl Acad Sci USA 90:572-576, 1993; S ymes et al,: Mol Endocrinol 8:1750-1763, 1994), To investigate the mec hanisms of action of CNTF in the CNS, we have analyzed the activation of STAT proteins in a septal-derived cell line, SN48, and in primary C NS cultures, CNTF treatment of SN48 cells produces a sustained activat ion of Stat3, CNTF treatment of SN48 cells also activated transcriptio n mediated by the VIP cytokine responsive element (CyRE) which contain s a STAT binding site, Mutation of the STAT site in the CyRE attenuate d transcriptional activation by CNTF, indicating the importance of STA T proteins to CNTF-dependent transcriptional activation in SN48 cells, In cultures of embryonic rat septum and other brain areas, in additio n to Stat3, CNTF also activates Stat1, As in cells of the PNS and non- neuronal cells, the Janus kinase (Jak)-STAT pathway is activated in CN S cells by cytokines, The SN48 cell line may be valuable in further ch aracterization of regulation of the Jak-STAT pathway by neuropoietic c ytokines. (C) 1996 Wiley-Liss, Inc.