MRE-binding transcription factor-1 is activated during endotoxemia: a central role for metallothionein

Endotoxin (LPS) has been established to induce hepatic rnetallothionein (NIT), 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 MREd-driven reporter gene. MTF-1 DNA-binding activity was increased 16-24 h after LIPS administration in wild-type mice. white no such activation was observed in MT-null mice during the same period. The expression of alpha(1)-acid gtycoprotein (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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.