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KMID : 1225120100020010031
Vascular Neurology
2010 Volume.2 No. 1 p.31 ~ p.36
Cytokine Mediated Induction of Metallothionein I & II in Oxygen-Glucose Deprived BV2 Cells
Kim Ji-Hyun

Kim Jong-Heon
Moon Che-Il
Han Hyung-Soo
Abstract
Objective: Metallothionein (MT) is a family of metal-binding cysteine-rich proteins with a neuroprotective function after brain injury. The functions of MT include detoxification of heavy metals, neutralization of free radicals, neurite outgrowth, regeneration, anti-apoptosis, and inflammation in neurological disorders such as the stroke. In this study, we investigated the effects of oxygen glucose deprivation (OGD)+reperfusion (Rep) on the regulation of MT expression in BV2 cells.

Methods: BV2 cells were exposed to hypoxia and ribonucleic acid (RNA) samples were extracted from the cells. Reverse transcription polymerase chain reaction was performed to observe the gene expression patterns of MT-1 & II, tumor necrosis factor (TNF)-¥á, interleukin-6 (IL-6), and IL-10. To determine correlation between these cytokines and MT messenger RNA (mRNA) expression, the cells were treated by pentoxifylline in order to inhibit TNF-¥á and neutralized by antibodies against IL-6 and IL-10.

Results: The levels of MT-I&II mRNA as well as pro- and anti-inflammatory cytokines (TNF-¥á, IL-6, and IL-10) were increased markedly in OGD+Rep conditioned BV2 cells during the acute phase. Inhibition of cytokines down-regulated the MT-I&II expression.

Conclusions: The results demonstrated that TNF-¥á could be an MT-I&II inducer and IL-10 may affect MT-II expression in early inflammation. These provide an insight into the mechanism involved in MT-induced neuroprotection against inflammation-mediated neurodegenerative diseases.
KEYWORD
CNS, Cytokine, Ischemia, Metallothionein, Penotoxifylline
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