p38 Mitogen-Activated Protein Kinase Modulates Expression of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Induced by Interferon-γ in Fetal Brain Astrocytes

This study describes the involvement of the p38 mitogen-activated protein kinase (MAPK) during interferon-γ (IFN-γ) signaling in fetal brain astrocytes. In some pathological conditions of brain, p38 MAPK transduces stress-related signals, increases expression of proinflammatory cytokines, and induces cellular damage or apoptosis. In astrocytes, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression level was increased by IFN-γ. AG490, a JAK inhibitor, blocked TRAIL expression induced by IFN-γ. SB203580, a specific p38α and p38β2 MAPK inhibitor, decreased the TRAIL expression induced by IFN-γ. The phosphorylation of the Ser727 site of STAT1, but not the Tyr701 site, was inhibited by SB203580. These results suggest that p38 MAPK modulates STAT1 phosphorylation in IFN-γ signaling in fetal brain astrocytes.