Src suppressed C kinase substrate regulates the lipopolysaccharide-induced TNF-alpha biosynthesis in rat astrocytes.

The protein kinase C (PKC) is known to be a critical component in the signaling cascades that lead to astrocyte-activation. To further understand the mechanism of PKC signaling in astrocyte-activation, we investigated the effect of SSeCKS, a PKC substrate, on LPS-induced cytokine expression in astrocytes by RT-PCR and enzyme-linked immunosorbent assay. Exposure of the cells to LPS induced rapid translocation of SSeCKS to the perinuclear sides, ERK activation and pronounced TNF-alpha production, which can be inhibited by the PKC inhibitor Gö6983. By using siRNA knockdown of SSeCKS expression, LPS-induced signaling events were partly inhibited, including ERK activation, inducible TNF-alpha biosynthesis and secretion. These results suggest that SSeCKS is involved in the LPS-induced TNF-alpha expression in astrocytes mediated by PKC.