Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line

Abstract Background The aim of this study is to examine the inflammatory-cytokine expressions in the presence of non-cytotoxic dose of methylmercury (MeHg) in murine macrophages, which is suspected to play an important role in brain damage caused by MeHg exposure. We focused on murine macrophage inf...

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Main Authors: Juliet David, Athira Nandakumar, Muflihatul Muniroh, Suminori Akiba, Megumi Yamamoto, Chihaya Koriyama
Format: Article
Language:English
Published: BMC 2017-11-01
Series:European Journal of Medical Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40001-017-0287-4
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author Juliet David
Athira Nandakumar
Muflihatul Muniroh
Suminori Akiba
Megumi Yamamoto
Chihaya Koriyama
author_facet Juliet David
Athira Nandakumar
Muflihatul Muniroh
Suminori Akiba
Megumi Yamamoto
Chihaya Koriyama
author_sort Juliet David
collection DOAJ
description Abstract Background The aim of this study is to examine the inflammatory-cytokine expressions in the presence of non-cytotoxic dose of methylmercury (MeHg) in murine macrophages, which is suspected to play an important role in brain damage caused by MeHg exposure. We focused on murine macrophage inflammatory protein-2 (MIP-2), keratinocyte chemoattractant (KC), and monocyte chemoattractant protein-5 (MCP-5). MIP-2 and KC are murine functional homologues of human IL-8 and MCP-5 for human MCP-1. Furthermore, we examined the suppressive effect of N-acetyl-l-cysteine (NAC) on the MeHg-induced inflammatory cytokines. Methods In a murine RAW264.7 macrophage cell line, MeHg-induced cytokine expressions were measured using real-time PCR. The suppressive effect of NAC was examined by putting it into the culture medium together with MeHg (co-treatment). In addition, pre- and post-treatment experiments were conducted, in which the cells were treated with NAC before and after MeHg exposure, respectively. Results Exposure to a non-cytotoxic dose of MeHg up-regulated the mRNA expression of MIP-2 and MCP-5. On the other hand, KC expression was not induced in the presence of MeHg. Effect of MeHg on MIP-2 expressions was suppressed by pre-, co-, and post-treatment with NAC. However, the suppressive effect of pre-treatment was less than the post-treatment, which was as effective as co-treatment. Conclusion In functional homologues of human IL-8, only MIP-2 expression, not KC, was activated in the presence of non-cytotoxic dose of MeHg in murine RAW264.7 macrophage cell line. The more evident inhibitory effect of NAC observed in post-treatment experiments suggests a possible involvement of intracellular activities such as antioxidant effects.
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spelling doaj.art-28316f9775134f03ab8eba57e14f02b62022-12-22T03:57:37ZengBMCEuropean Journal of Medical Research2047-783X2017-11-012211810.1186/s40001-017-0287-4Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell lineJuliet David0Athira Nandakumar1Muflihatul Muniroh2Suminori Akiba3Megumi Yamamoto4Chihaya Koriyama5Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental SciencesDepartment of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental SciencesIntegrated Physiology Section, Department of Basic Medical Science, National Institute for Minamata DiseaseDepartment of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental SciencesAbstract Background The aim of this study is to examine the inflammatory-cytokine expressions in the presence of non-cytotoxic dose of methylmercury (MeHg) in murine macrophages, which is suspected to play an important role in brain damage caused by MeHg exposure. We focused on murine macrophage inflammatory protein-2 (MIP-2), keratinocyte chemoattractant (KC), and monocyte chemoattractant protein-5 (MCP-5). MIP-2 and KC are murine functional homologues of human IL-8 and MCP-5 for human MCP-1. Furthermore, we examined the suppressive effect of N-acetyl-l-cysteine (NAC) on the MeHg-induced inflammatory cytokines. Methods In a murine RAW264.7 macrophage cell line, MeHg-induced cytokine expressions were measured using real-time PCR. The suppressive effect of NAC was examined by putting it into the culture medium together with MeHg (co-treatment). In addition, pre- and post-treatment experiments were conducted, in which the cells were treated with NAC before and after MeHg exposure, respectively. Results Exposure to a non-cytotoxic dose of MeHg up-regulated the mRNA expression of MIP-2 and MCP-5. On the other hand, KC expression was not induced in the presence of MeHg. Effect of MeHg on MIP-2 expressions was suppressed by pre-, co-, and post-treatment with NAC. However, the suppressive effect of pre-treatment was less than the post-treatment, which was as effective as co-treatment. Conclusion In functional homologues of human IL-8, only MIP-2 expression, not KC, was activated in the presence of non-cytotoxic dose of MeHg in murine RAW264.7 macrophage cell line. The more evident inhibitory effect of NAC observed in post-treatment experiments suggests a possible involvement of intracellular activities such as antioxidant effects.http://link.springer.com/article/10.1186/s40001-017-0287-4InflammationMethylmercuryRAW264.7 cell lineN-acetyl-l-cysteineMacrophage inflammatory protein-2Keratinocyte chemoattractant
spellingShingle Juliet David
Athira Nandakumar
Muflihatul Muniroh
Suminori Akiba
Megumi Yamamoto
Chihaya Koriyama
Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line
European Journal of Medical Research
Inflammation
Methylmercury
RAW264.7 cell line
N-acetyl-l-cysteine
Macrophage inflammatory protein-2
Keratinocyte chemoattractant
title Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line
title_full Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line
title_fullStr Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line
title_full_unstemmed Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line
title_short Suppression of methylmercury-induced MIP-2 expression by N-acetyl-l-cysteine in murine RAW264.7 macrophage cell line
title_sort suppression of methylmercury induced mip 2 expression by n acetyl l cysteine in murine raw264 7 macrophage cell line
topic Inflammation
Methylmercury
RAW264.7 cell line
N-acetyl-l-cysteine
Macrophage inflammatory protein-2
Keratinocyte chemoattractant
url http://link.springer.com/article/10.1186/s40001-017-0287-4
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