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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 NaAsO2 intra-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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Duan X,Gao S,Li J,Wu L,Zhang Y,Li W,Zhao L,Chen J,Yang S,Sun G,Li B

doi

10.1016/j.molimm.2016.12.005

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

160-172

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(16)30265-6

journal_volume

pub_type

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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.