Cytokine-mediated induction of metallothionein in Hepa-1c1c7 cells by oleanolic acid.
Oleanolic acid (OA), a pentacyclic triterpene acid, has been reported to possess inducing activity of hepatic metallothionein (MT). However, the mechanism underlying its effects is unknown. This study investigated the effects of OA on the regulation of MT expression in an in vitro model. OA 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 OA-treated conditioned media from the RAW 264.7 cells. Co-treating the RAW 264.7 cells with OA and pentoxifylline, a TNF-alpha synthesis inhibitor, resulted in a decrease in the effects of OA on the MT induction. In the OA-exposed RAW 264.7 cell cultures, production and mRNA levels of TNF-alpha and IL-6 were increased. However, the MT induction activity was inhibited when antibodies to TNF-alpha and/or IL-6 were added to the OA-treated conditioned media from the RAW 264.7 cells. These results suggest that the up-regulation of MT expression by OA was mediated by the TNF-alpha and IL-6 released from UA-activated macrophages.
Kim
Ji Young
JY
Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Kwangju 501-759, Republic of Korea.
Lee
Kyung Jin
KJ
Kim
Dong Hee
DH
Jeong
Tae Cheon
TC
Lee
Eung Seok
ES
Choi
Young Muk
YM
Jeong
Hye Gwang
HG
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D009828:Oleanolic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009828:Oleanolic Acid; D008668:Metallothionein