Src suppressed C kinase substrate regulates the lipopolysaccharide-induced TNF-α 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 enzymelinked immunosorbent assay. Exposure of the cells to LPS induced rapid translocation of SSeCKS to the perinuclear sides, ERK activation and pronounced TNF-a production, which can be inhibited by the PKC inhibitor Go6983. By using siRNA knockdown of SSeCKS expression, LPSinduced signaling events were partly inhibited, including ERK activation, inducible TNF-a biosynthesis and secretion. These results suggest that SSeCKS is involved in the LPS-induced TNF-oc expression in astrocytes mediated by PKC.