Cytokine regulation of PS2 gene expression in mouse astrocytes

Treatment of astrocytes with interleukin (IL)-6, -7 and tumor necrosis factor (TNF)-alpha produced a marked increase in the expression of the pS2 gene, an estrogen-inducible gene originally identified in the human breast cancer cell line MCF-7. The effect of IL-6 and TNF-alpha was completely inhibited by the addition of anti-IL-6 monoclonal antibody and anti-TNF-alpha monoclonal antibody, respectively. During the treatment with IL-6 and TNF-alpha, neither increase in thymidine incorporation nor morphological change was observed. Inhibition of protein synthesis by cycloheximide and inhibition of RNA synthesis by actinomycin D abrogated the stimulatory effect on pS2 mRNA expression of IL-6 and TNF-alpha, suggesting that new protein synthesis as well as new RNA synthesis was required for their action. These results suggest that brain injury trigger pS2 gene expression in astrocytes through the induction of cytokines.