Arsenic trioxide mediates HAPI microglia inflammatory response and the secretion of inflammatory cytokine IL-6 via Akt/NF-κB signaling pathway.
Arsenic is a widely distributed toxic metalloid in around the world. Inorganic arsenic species are deemed to affect astrocytes functions and to cause neuron apoptosis. Microglia are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA and reverse transcriptase PCR (RT-PCR), we showed that Arsenic trioxide up-regulated the expression and secretion of IL-6 in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. These pro-inflammatory responses were inhibited by the Akt blocker, LY294002. Further, Arsenic trioxide exposure could induce phospho rylationand degradation of IкBα, and the translocation of NF-κB p65 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the NF-кB signaling pathway can be activated after Arsenic trioxide treatment. Besides, Akt blocker LY294002 also obviously attenuated NF-кB activation and transnuclear induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of pro-inflammatory cytokine and NF-кB activation induced by Arsenic trioxide can be mediated by elevation of p-Akt in HAPI microglia cells.
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Gang
G
Chen
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Jiamin
J
Mao
Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Jianmei
J
Zhao
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Yan
Y
Zhang
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Ting
T
Li
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Cheng
C
Wang
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Lingfei
L
Xu
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Qiaoyun
Q
Hu
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Xiaoke
X
Wang
Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Shengyang
S
Jiang
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Xiaoke
X
Nie
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China. Electronic address: wqy@ntu.edu.cn.
Qiyun
Q
Wu
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002478:Cells, Cultured; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D015850:Interleukin-6; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D001151:Arsenic
Akt/NF-кB/IL-6; Arsenic trioxide; Microglia