[Cytokine-induced metallothionein expression and modulation of cytokine expression by metallothionein].
A multifunctional protein metallothionein (MT) is induced by various chemicals and cytokines. We have found novel functions of MT as follows: 1) Cytokine expression such as IL-1alpha, IL-6, and TNFalpha responding to lipopolysaccharide is reduced in MT-deficient macrophages compared with in wild-type cells. 2) Nitric oxide production responding to TNFalpha and LPS is reduced in MT-deficient macrophages compared with in wild-type cells. 3) M-CSF expression responding to zinc is reduced in MT-deficient fibroblasts compared with in wild-type cells, and increased in MT-overexpressed fibroblasts compared with in control cells. 4) LIF, a STAT3 activating cytokine, protects the heart from ischemia/reperfusion injury. Transgenic mice overexpressing STAT3 have tolerance to ischemia/reperfusion-induced damage, whereas MT-null mutation cancels the myocardial protection. In this review, we discuss the relation of MT and stress responses from the point of view of cytokine-induced expression of MT and modulation of cytokine expression by MT.
Itoh
Norio
N
Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita City, Japan. n-itoh@phs.osaka-u.ac.jp
Kimura
Tomoki
T
D000210:Acute-Phase Reaction; D000818:Animals; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D015850:Interleukin-6 / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008668:Metallothionein / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D008668:Metallothionein