Methylmercury induces a brain-specific increase in chemokine CCL4 expression in mice

Abstract

-Expression of the chemokine genes Ccl2, Ccl4, Ccl7, Ccl9, and Ccl12 is increased in cerebellum of mice treated with methylmercury. To investigate the effect of methylmercury on other tissues and organs, levels of chemokine mRNA were investigated in mouse cerebrum, kidney, liver, and spleen. In cerebrum, expression levels of the five chemokines were significantly increased after methylmercury treatment. In kidney, expression levels of Ccl2, Ccl7, Ccl9, and Ccl12, but not Ccl4 were increased. No significant effects were seen on mRNA levels of the chemokines in liver and spleen. Thus, although methylmercury increases the expression levels of multiple chemokines in the brain and kidney, expression of Ccl4 increases only in the brain. Hence, this phenomenon may be involved in methylmercury toxicity specific to the central nervous system.

<i>S</i>-Mercuration of cellular proteins by methylmercury and its toxicological implications

“…The biological factors that are altered by MeHg have been explored with the aim of shedding light on the molecular mechanisms that underlie MeHg toxicity (Hwang et al, 2011a(Hwang et al, , 2013aHwang and Naganuma, 2006;Kim et al, 2012Kim et al, , 2013Lee et al, 2012;Takahashi et al, 2013;Toyama et al, 2011). Furthermore, the research group led by Dr. Naganuma has found a large number of proteins that are resistant or hypersensitive to MeHg (Hwang et al, 2007(Hwang et al, , 2010a(Hwang et al, , 2010b(Hwang et al, , 2010c(Hwang et al, , 2011b(Hwang et al, , 2012a(Hwang et al, , 2012b(Hwang et al, , 2013b.…”

Methylmercury induces expression of interleukin-1β and interleukin-19 in mice brains

“…We analyzed expression variation of gene clusters in the brain of mice treated with methylmercury, identifying 2 chemokines (CCL3 and CCL4) as genes whose expression is increased by methylmercury in the brain (Lee et al, 2012;Kim et al, 2013). Methylmercury has also been reported to induce the expression of interleukin IL-6, a kind of cytokine (Chang, 2007;Noguchi et al, 2013).…”

Effect of Metallothionein-III on Mercury-Induced Chemokine Gene Expression

“…Mercury compounds, such as methylmercury and mercury vapor, are harmful substances that cause disorders of the CNS, but the influence of MT-III on the disorders caused by these mercuric compounds is poorly understood. Recently, methylmercury has been reported to increase expression of the chemokine genes, Ccl3 , Ccl4 , Ccl7 , Ccl12 and Cxcl10 in the mouse brain [ 20 , 21 , 27 ]. The most highlighted knowledge in this study is that Ccl3 expression in the cerebrum and the cerebellar expression of Ccl12 and Cxcl10 were significantly different between wild-type mice and MT-III null mice only in the methylmercury exposure.…”

“…Accordingly, the expression of several chemokines increases with hypoglossal nerve damage, however the role of chemokines in cranial nerves remains unclear. Methylmercury induces a brain-specific increase in Ccl4 expression in mice [ 21 ]. In addition, it is assumed that CCL4 is involved in the pathway mediating the toxicity of methylmercury in the CNS [ 33 , 34 ].…”

“…Recently, it has been reported that methylmercury increases the expression of several chemokine genes specific to the mouse brain [ 20 ]. Furthermore, we examined the impact of methylmercury on the expression of chemokine genes in various mouse tissues and found that expression of Ccl4 shows brain specific induction by methylmercury treatment [ 21 ]. Chemokines are a type of cytokine known to cause migration of leukocytes.…”