Regulation of cell cycle proteins by TNF-alpha and TGF-beta in cells of oligodendroglial lineage

Proliferation and apoptosis are two dynamic, interrelated processes that ar e regulated by growth factors and cytokines. We investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-bet a (TGF-beta) on apoptosis and regulation of cell cycle proteins in OLG line age cells. We found that: (1) both cytokines enhanced apoptosis in neonatal pre-OLGs but only TNF alpha-nnediated apoptosis persisted in the presence of a mitogen, fibroblast growth factor (FGF); (2) cell cycle proteins such as p21(waf1/cip1), p27(kip1) cyclin D1 and PCNA were differentially regulat ed by TNF-alpha and TGF-beta. We conclude that differential modulation of c ell cycle proteins by TNF-alpha and TGF-beta contributes to the diversity o f their biological effects in OLG lineage cells. (C) 2000 Elsevier Science B.V. All rights reserved.