MRE-binding transcription factor-1 is activated during endotoxemia: a central role for metallothionein.
Endotoxin (LPS) has been established to induce hepatic metallothionein (MT), but the specific role of MT remains unknown. In this study, we examined whether MT can modulate MTF-1 activity during endotoxemia. Treatment with IL-6, the main mediator of MT induction during endotoxemia, enhanced the expression of the MRE(d)-driven reporter gene. MTF-1 DNA-binding activity was increased 16-24 h after LPS administration in wild-type mice, while no such activation was observed in MT-null mice during the same period. The expression of alpha(1)-acid glycoprotein (AGP) mRNA, an RNA regulated by MTF-1, was lower in MT-null than in wild-type mice. Our results suggested that MTF-1 was activated during endotoxemia. MT can act as an activator of MTF-1, and MT can induce MTF-1 targeted gene expression during endotoxemia.
Kimura
Tomoki
T
Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka 565-0871, Japan.
Itoh
Norio
N
Takehara
Miyako
M
Oguro
Ikuyo
I
Ishizaki
Jun-ichi
J
Nakanishi
Tsuyoshi
T
Tanaka
Keiichi
K
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009961:Orosomucoid / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D000097809:Transcription Factor MTF-1
D004247:DNA; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008668:Metallothionein; D009961:Orosomucoid; D012333:RNA, Messenger; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1