Inorganic mercury‑induced MIP‑2 expression is suppressed by N‑acetyl‑L‑cysteine in RAW264.7 macrophages

David,Juliet; Muniroh,Muflihatul; Nandakumar,Athira; Tsuji,Mayumi; Koriyama,Chihaya; Yamamoto,Megumi

doi:10.3892/br.2019.1263

Inorganic mercury‑induced MIP‑2 expression is suppressed by N‑acetyl‑L‑cysteine in RAW264.7 macrophages

Authors:
- Juliet David
- Muflihatul Muniroh
- Athira Nandakumar
- Mayumi Tsuji
- Chihaya Koriyama
- Megumi Yamamoto
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Affiliations: Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan, Department of Environmental Health, University of Occupational and Environmental Health, Kitakyusyu, Fukuoka 807‑8555, Japan, Department of Environment and Public Health, National Institute for Minamata Disease, Minamata, Kumamoto 867‑0008, Japan
Published online on: December 3, 2019 https://doi.org/10.3892/br.2019.1263
Pages: 39-45
Copyright: © David et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophages play an important role in neurotoxicity caused by methylmercury exposure through inflammatory responses. Methylmercury is known to demethylate to inorganic mercury in the brain, and macrophages are likely to be involved in this process. However, the inflammatory responses of macrophages against exposure to inorganic mercury are unclear. In the present study, inflammatory cytokine expression profiles were examined in the presence of non‑toxic doses of inorganic mercury (Hg2+) using RAW264.7 macrophages, focusing on the expression of C‑X‑C motif chemokine 2 (MIP‑2)/platelet‑derived growth factor‑inducible protein KC (KC) and C‑C motif chemokine 12 (MCP‑5). Furthermore, the suppressive effect of N‑acetyl‑L‑cysteine (NAC) on inorganic mercury‑induced MIP‑2 expression was also examined. Inorganic mercury‑induced mRNA expression was measured using reverse transcription‑quantitative PCR. The mRNA expression of MIP‑2 and MCP‑5 was significantly upregulated by exposure to 20 µM Hg2+ (non‑toxic levels), but not that of KC. The suppressive effect of NAC on these cytokine expression levels was examined by its addition to the culture medium together with Hg2+ (co‑treatment), and pre‑ and post‑treatments in which the cells were treated with NAC before and after Hg2+ exposure, respectively. Hg2+‑upregulated MIP‑2 expression was suppressed by NAC regardless of the time sequence of the treatment, suggesting that the suppressive role of NAC in Hg2+‑induced inflammation manifests as a possible chelator and antioxidant/reactive oxygen species scavenger.

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