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 are regulated by growth factors and cytokines. We investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) on apoptosis and regulation of cell cycle proteins in OLG lineage cells. We found that: (1) both cytokines enhanced apoptosis in neonatal pre-OLGs but only TNFalpha-mediated 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 regulated by TNF-alpha and TGF-beta. We conclude that differential modulation of cell cycle proteins by TNF-alpha and TGF-beta contributes to the diversity of their biological effects in OLG lineage cells.