Methylmercury induces CCL2 expression through activation of NF-κB in human 1321N1 astrocytes

被引:25
作者
Kim, Min-Seok [1 ]
Takahashi, Tsutomu [1 ]
Lee, Jin-Yong [1 ,2 ]
Hwang, Gi-Wook [1 ]
Naganuma, Akira [1 ]
机构
[1] Tohoku Univ, Lab Mol & Biochem Toxicol, Grad Sch Pharmaceut Sci, Sendai, Miyagi 9808578, Japan
[2] Aichi Gakuin Univ, Lab Pharmaceut Hlth Sci, Sch Pharm, Chikusa Ku, Nagoya, Aichi 4648650, Japan
关键词
Methylmercury; Chemokine; CCL2; NF-kappa B; GENE-EXPRESSION; CHEMOKINE; TOXICITY; CELLS;
D O I
10.2131/jts.37.1275
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Methylmercury is an environmental pollutant that is toxic to the central nervous system; however, the molecular mechanisms underlying its toxicity remain unclear. Methylmercury increases expression of several chemokines in the cerebellum of mice treated with methylmercury. The present study analyzes the mechanism underlying methylmercury-induced chemokine expression using human 1321N1 astrocytes, and shows that methylmercury increases CCL2 expression in these cells. The transcription factor NF-kappa B is involved in the induction of chemokine expression. Methylmercury increased the level of the NF-kappa B p65 subunit in the nuclei of 1321N1 cells. The methylmercury-induced increase in CCL2 expression was significantly decreased by suppression of p65 expression by RNA interference. These results suggest that methylmercury induces chemokine expression through activation of NF-kappa B in human astrocytes.
引用
收藏
页码:1275 / 1278
页数:4
相关论文
共 15 条
[1]  
Castoldi Anna F, 2003, Rev Environ Health, V18, P19
[2]   Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun-N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain [J].
Fujimura, Masatake ;
Usuki, Fusako ;
Sawada, Masumi ;
Takashima, Akihiko .
NEUROTOXICOLOGY, 2009, 30 (06) :1000-1007
[3]   NF-κB and rel proteins:: Evolutionarily conserved mediators of immune responses [J].
Ghosh, S ;
May, MJ ;
Kopp, EB .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :225-260
[4]   Estradiol inhibits ongoing autoimmune neuroinflammation and NFκB-dependent CCL2 expression in reactive astrocytes [J].
Giraud, Sebastien N. ;
Caron, Cecile M. ;
Pham-Dinh, Danielle ;
Kitabgi, Patrick ;
Nicot, Arnaud B. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (18) :8416-8421
[5]   The Chemokine CCL2 Protects Against Methylmercury Neurotoxicity [J].
Godefroy, David ;
Gosselin, Romain-Daniel ;
Yasutake, Akira ;
Fujimura, Masatake ;
Combadiere, Christophe ;
Maury-Brachet, Regine ;
Laclau, Muriel ;
Rakwal, Randeep ;
Melik-Parsadaniantz, Stephane ;
Bourdineaud, Jean-Paul ;
Rostene, William .
TOXICOLOGICAL SCIENCES, 2012, 125 (01) :209-218
[6]   Resistance of human brain microvascular endothelial cells in culture to methylmercury: cell-density-dependent defense mechanisms [J].
Hirooka, Takashi ;
Fujiwara, Yasuyuki ;
Shinkai, Yasuhiro ;
Yamamoto, Chika ;
Yasutake, Akira ;
Satoh, Masahiko ;
Eto, Komyo ;
Kaji, Toshiyuki .
JOURNAL OF TOXICOLOGICAL SCIENCES, 2010, 35 (03) :287-294
[7]   Circuitry of nuclear factor κB signaling [J].
Hoffmann, A ;
Baltimore, D .
IMMUNOLOGICAL REVIEWS, 2006, 210 :171-186
[8]   Inhibition of F-box protein FBXO6 gene expression by RNA interference enhances cadmium toxicity in HEK293 cells [J].
Hwang, Gi-Wook ;
Du, Ke ;
Takahashi, Tsutomu ;
Naganuma, Akira .
JOURNAL OF TOXICOLOGICAL SCIENCES, 2011, 36 (06) :847-849
[9]   Gene expression profiling using DNA microarray analysis of the cerebellum of mice treated with methylmercury [J].
Hwang, Gi-Wook ;
Lee, Jin-Yong ;
Ryoke, Katsunori ;
Matsuyama, Fujio ;
Kim, Jong-Mu ;
Takahashi, Tsutomu ;
Naganuma, Akira .
JOURNAL OF TOXICOLOGICAL SCIENCES, 2011, 36 (03) :389-391
[10]   Amyloid-β peptides induce several chemokine mRNA expressions in the primary microglia and Ra2 cell line via the PI3K/Akt and/or ERK pathway [J].
Ito, Sachiko ;
Sawada, Makoto ;
Haneda, Masataka ;
Ishida, Yoshiyuki ;
Isobe, Ken-ichi .
NEUROSCIENCE RESEARCH, 2006, 56 (03) :294-299