Abstract:
:Ursolic acid (UA), a pentacyclic triterpene acid, is reported to have inducing activity of hepatic metallothionein (MT) which responsible for the detoxification of heavy metals; however, the mechanism underlying its effects is poorly understood. To further determine the underlying mechanism of UA, this study investigated the effects of UA on the induction of hepatic MT expression in an in vitro model, using murine hepatoma cell line Hepa-1c1c7 and murine macrophage cell line RAW 264.7 cell cultures. The UA added directly to Hepa-1c1c7 cells had no effect on MT induction. However, MT and its mRNA levels were markedly increased when Hepa-1c1c7 cells were cultured with UA-treated conditioned media from RAW 264.7. Concomitant treatment with UA and pentoxifylline, a TNF-alpha synthesis inhibitor, to RAW 264.7 cells decreased the effects of UA on the MT induction. In UA-exposed RAW 264.7 cell cultures, TNF-alpha and IL-6 production and TNF-alpha and IL-6 mRNA levels increased. When antibodies to TNF-alpha or/and IL-6 were added to UA-treated conditioned media from RAW 264.7, the MT induction activity was inhibited. These results demonstrate that UA induces hepatic MT expression through TNF-alpha and IL-6 released from UA-activated macrophages, which may be the mechanism, whereby UA elicits its biological effects.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Jeong HG,Kim HG,Hwang YPdoi
10.1016/j.toxlet.2004.11.002keywords:
subject
Has Abstractpub_date
2005-03-15 00:00:00pages
369-76issue
3eissn
0378-4274issn
1879-3169pii
S0378-4274(04)00504-1journal_volume
155pub_type
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