The accumulation of macrophages has been observed around lesions of the brain in patients with
Minamata disease. In this condition,
mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated. Here, we investigated how MeHg affects the expression of proinflammatory
cytokines such as
interleukin (IL)-6 and
IL-8 in cultured human U937 macrophages. Compared with controls,
IL-6 and
IL-8 mRNA expression was maximally induced in U937 macrophages
after treatment with 10 μM MeHg for 6 h. The
protein secretion of
IL-6 and
IL-8 was significantly stimulated by MeHg in U937 macrophages. Results from
luciferase reporter assay indicated functional activation of
nuclear factor kappa B and the involvement of subunit RelA and p50 in MeHg-induced
IL-6 and
IL-8 activation, which was confirmed by
siRNA knockdown experiments. MeHg exposure at 4 μM also significantly induced
IL-8 expression in U-87 MG cells at
mRNA and
protein level, indicating that
IL-8 induction might be a general mode of action of MeHg treatment among different cell types. These results indicate a possible involvement of an early inflammatory response, including
IL-6 and
IL-8 expression in the pathogenesis of MeHg.
N-acetyl-l-cysteine suppressed MeHg-induced activation of
IL-6 and
IL-8 mRNA expression in U937 macrophages, indicating the effectiveness of
N-acetyl-l-cysteine as a therapeutic drug in MeHg-induced
inflammation. Copyright © 2016 John Wiley & Sons, Ltd.