title: Acute arsenic exposure induces inflammatory responses and CD4+T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2.
abstract: Increasing lines of evidence indicate that arsenic may be associated with immune related problems, but its detailed effects on immune organs are poorly understood. The objective of this study was to explore inflammatory responses and T cell differentiation of arsenic exposure in spleen and thymus. Female C57BL/6 mice were used as a model to systemically administration 2.5, 5 and 10mg/kg NaAsO2intra-gastrically for 24h. We found that arsenic significantly decreased the spleen and thymus weights and indices, and flow cytometry revealed that arsenic decreased the relative frequency of CD4+T cell subpopulation and the ratios of CD4/CD8 in spleen. In contrast, serum concentration of tumor necrosis factor α (TNF-α), IL-1β and IL-6 as well as the mRNA of key inflammatory mediators in spleen and thymus, including transforming growth factor β (Tgf-β), Tnf-α, Il-12, Il-1β and Il-6 were significantly increased in arsenic-treated mice compared to the control as assayed by ELISA and real time PCR, respectively. In addition, arsenic increased the expression of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) -associated transcription factors and cytokines as well as decreased Th17-associated transcription factors and cytokines. Moreover, arsenic enhanced oxidative stress and induced the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 and their downstream transcription factors nuclear factor kappa B (NF-kB) and nuclear factor E2-related factor 2 (Nrf2), which comprise important mechanistic pathways involved in immune-inflammatory manifestations. Together, these results provide a novel strategy to block the arsenic-dependent impairments in immune responses.
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, 110013 Shenyang, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Gao
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Periodontics, Shenyang Stomatological Hospital, Shenyang 110002, China.
authors.forename: Liuzhong
authors.initials: L
authors.lastname: Wu
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Chen
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Environment and Non-Communicable Diseases Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. Electronic address: bli10@cmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D001151:Arsenic
keywords: Arsenic; Immunomodulation; Inflammation; MAPK; Nrf2; Oxidative stress