Involvement of Cytokines in the Hepatic Metallothionein Expression by α-Hederin

Abstract

α-Hederin, a triterpenoid saponin, has been reported to induce hepatic metallothionein (MT). However, the mechanism underlying its effects is unknown. This study investigated the effects of α-hederin on the regulation of MT expression in an in vitro model using the murine hepatoma cell line, Hepa-1c1c7, and the murine macrophage cell line, RAW 264.7. α-Hederin that was added directly to Hepa-1c1c7 cells had no effect on MT induction. However, MT and its mRNA levels increased markedly when the Hepa-1c1c7 cells were cultured with the α-hederin-treated, conditioned medium from the RAW 264.7 cells. Co-treating the RAW 264.7 cells with α-hederin and pentoxifylline, a TNF-α synthesis inhibitor, resulted in decreased effects of α-hederin on MT induction. In the α-hederin-exposed RAW 264.7 cell cultures, production and mRNA levels of TNF-α and IL-6 were increased. Accordingly, it was found that the MT induction activity was inhibited when antibodies to TNF-α and/or IL-6 were added to the α-hederin-treated, conditioned medium from the RAW 264.7 cells. These results suggest that the upregulation of MT expression by α-hederin is mediated by TNF-α and IL-6.

Key words

α-Hederin - metallothionein - TNF-α - IL-6 - hepatoma - macrophages

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1 * These two authors contributed equally to this work.