The effect of cytokines on the expression of selenoprotein P (SeP) in the human liver cell line HepG2 was investigated. Treatment with interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha had no effect on SeP levels in culture media or on SeP mRNA expression. Conversely, Western analysis revealed a dose-dependent reduction of SeP content in culture medium after treatment with transforming growth factor (TGF)-beta1 with an 1C50 of 31 pM. Treatment with 100 pM TGF-51 for 48 h led to a decrease to 21 +/- 9% of controls. RT-PCR analysis of SeP mRNA expression demonstrated an inhibition of SeP transcription to 40+/-2% of control levels after 24 h. The expression of a luciferase reporter construct under control of the human SeP promoter was downregulated by TGF-beta1 treatment in a dose-dependent fashion indicating a transcriptional regulation of the SeP gene by TGF-beta1.