期刊
MOLECULAR IMMUNOLOGY
卷 81, 期 -, 页码 160-172出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2016.12.005
关键词
Arsenic; Inflammation; Immunomodulation; Oxidative stress; MAPK; Nrf2
资金
- National Natural Science Foundation of China (NSFC) [81673114]
- Key Laboratory Basic Research Funds from Liaoning Education Department [LS201607]
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 10 mg/kg NaAsO2 intra-gastrically for 24 h. 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 alpha (TNF-alpha), IL-1 beta and IL-6 as well as the mRNA of key inflammatory mediators in spleen and thymus, including transforming growth factor beta (Tgf-beta), Tnf-alpha, Il-12, Il-1 beta 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 Thl 7-associated transcription factors and cytokines. Moreover, arsenic enhanced oxidative stress and induced the activation of extracellularsignal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases UNK) 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. (C) 2016 Elsevier Ltd. All rights reserved.
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