Chemokine CCL4 induced in mouse brain has a protective role against methylmercury toxicity

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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Methylmercury (MeHg) is selectively toxic to the central nervous system, but mechanisms related to its toxicity are poorly understood. In the present study, we identified the chemokine, C-C motif Chemokine Ligand 4 (CCL4), to be selectively upregulated in the brain of MeHg-administered mice. We then investigated the relationship between CCL4 expression and MeHg toxicity using in vivo and in vitro approaches. We confirmed that in C17.2 cells (a mouse neural stem cell line) and the mouse brain, induction of CCL4 expression occurs prior to cytotoxicity caused by MeHg. We also show that the addition of recombinant CCL4 to the culture medium of mouse primary neurons attenuated MeHg toxicity, while knockdown of CCL4 in C17.2 cells resulted in higher MeHg sensitivity compared with control cells. These results suggest that CCL4 is a protective factor against MeHg toxicity and that induction of CCL4 expression is not a result of cytotoxicity by MeHg but is a protective response against MeHg exposure.

Original languageEnglish
Article number36
Issue number3
Publication statusPublished - 2018 Jul 7


  • Brain
  • CCL4
  • Chemokine
  • Methylmercury


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