Involvement of cytokines in the hepatic metallothionein expression by alpha-hederin.
Alpha-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 alpha-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. Alpha-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 alpha-hederin-treated, conditioned medium from the RAW 264.7 cells. Co-treating the RAW 264.7 cells with alpha-hederin and pentoxifylline, a TNF-alpha synthesis inhibitor, resulted in decreased effects of alpha-hederin on MT induction. In the alpha-hederin-exposed RAW 264.7 cell cultures, production and mRNA levels of TNF-alpha and IL-6 were increased. Accordingly, it was found that the MT induction activity was inhibited when antibodies to TNF-alpha and/or IL-6 were added to the alpha-hederin-treated, conditioned medium from the RAW 264.7 cells. These results suggest that the upregulation of MT expression by alpha-hederin is mediated by TNF-alpha and IL-6.
Kim
Ji Young
JY
Department of Pharmacy, College of Pharmacy, Chosun University, Kwangju, South Korea.
Choi
Chul Yung
CY
Jeong
Hye Gwang
HG
D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008668:Metallothionein / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; C010177:beta-hederin; D009828:Oleanolic Acid; D008668:Metallothionein