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Toxics 2018, 6(3), 36;

Chemokine CCL4 Induced in Mouse Brain Has a Protective Role against Methylmercury Toxicity

Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan
Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Korea
Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Onogawa 16-2, Tsukuba, Ibaraki 305-8506, Japan
Department of Basic Medical Science, National Institute for Minamata Disease, Kumamoto 867-0008, Japan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 4 June 2018 / Revised: 23 June 2018 / Accepted: 5 July 2018 / Published: 7 July 2018
(This article belongs to the Special Issue Mercury and Methylmercury Toxicology and Risk Assessment)
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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. View Full-Text
Keywords: methylmercury; brain; chemokine; CCL4 methylmercury; brain; chemokine; CCL4

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Takahashi, T.; Kim, M.-S.; Iwai-Shimada, M.; Fujimura, M.; Toyama, T.; Naganuma, A.; Hwang, G.-W. Chemokine CCL4 Induced in Mouse Brain Has a Protective Role against Methylmercury Toxicity. Toxics 2018, 6, 36.

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