TGF beta 1 and TNF alpha potentiate nitric oxide production in astrocyte cultures by recruiting distinct subpopulations of cells to express NOS-2.

Nitric oxide (NO) synthase-2 (NOS-2), a key source of NO at sites of neuroinflammation, is induced in astrocyte cultures treated with lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma). A recent study examining the regulation of astrocytic NOS-2 expression demonstrated that transforming growth factor-beta1 (TGF beta 1) potentiated LPS plus IFN gamma-induced NOS-2 expression via expansion of the pool of astrocytes that express NOS-2. Results in the current report indicate that this population-based mechanism of increasing NOS-2 expression is not restricted to TGF beta 1, since it also accounts for the potentiation of NO production in astrocyte cultures by tumor necrosis factor-alpha (TNFalpha).