Methylmercury induces the expression of TNF-α selectively in the brain of mice

Miyuki Iwai-Shimada, Tsutomu Takahashi, Min Seok Kim, Masatake Fujimura, Hitoyasu Ito, Takashi Toyama, Akira Naganuma, Gi Wook Hwang

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Abstract

Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-α expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-α expression was induced to a greater extent in brain. Thus, it is possible that there may exist a selective mechanism by which methylmercury induces TNF-α expression in the brain. We also found that TNF-α expression was induced by methylmercury in C17.2 cells (mouse neural stem cells) and NF-κ B may participate as a transcription factor in that induction. Further, we showed that the addition of TNF-α antagonist (WP9QY) reduced the toxicity of methylmercury to C17.2 cells. In contrast, the addition of recombinant TNF-α to the culture medium decreased the cell viability. We suggest that TNF-α may play a part in the selective damage of the CNS by methylmercury. Furthermore, our results indicate that the higher TNF-α expression induced by methylmercury maybe the cause of cell death, as TNF-α binds to its receptor after being released extracellularly.

Original languageEnglish
Article number38294
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Dec 2

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    Iwai-Shimada, M., Takahashi, T., Kim, M. S., Fujimura, M., Ito, H., Toyama, T., Naganuma, A., & Hwang, G. W. (2016). Methylmercury induces the expression of TNF-α selectively in the brain of mice. Scientific reports, 6, [38294]. https://doi.org/10.1038/srep38294