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Involvement of cytokines in the hepatic metallothionein expression by alpha-hederin.

Abstract
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.
AuthorsJi Young Kim, Chul Yung Choi, Hye Gwang Jeong
JournalPlanta medica (Planta Med) Vol. 71 Issue 8 Pg. 743-7 (Aug 2005) ISSN: 0032-0943 [Print] Germany
PMID16142639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Interleukin-6
  • RNA, Messenger
  • Saponins
  • Tumor Necrosis Factor-alpha
  • beta-hederin
  • Oleanolic Acid
  • Metallothionein
Topics
  • Animals
  • Cell Line, Tumor (drug effects)
  • Cell Survival
  • Cytokines (biosynthesis)
  • Dose-Response Relationship, Drug
  • Interleukin-6 (biosynthesis)
  • Macrophages (drug effects, metabolism)
  • Metallothionein (drug effects, metabolism)
  • Mice
  • Oleanolic Acid (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
  • Phytotherapy
  • Plants, Medicinal
  • RNA, Messenger (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saponins (administration & dosage, pharmacology, therapeutic use)
  • Tumor Necrosis Factor-alpha (biosynthesis)

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