Abstract
BackgroundArsenic exposure has become a matter of worldwide concern, which is associated with immune-related diseases. However, little is known about its effect on inflammatory immune-related homeostasis. The purpose of our study was to understand the potential tuning of above responses exerted by chronic arsenic exposure.MethodsKunming mice were treated with 25 and 50 mg/L sodium arsenite for 1, 3 and 12 months via drinking water. At different endpoints of arsenic exposure, all animals and the whole spleen of the mice were weighed. The total arsenic levels of spleen were determined by the HPLC-HG-AFS method. Splenic NF-κB, MAPK and NRF2 protein levels by treatment of 25 mg/L NaAsO2 for 1, 3 and 12 months and 25 mg/L and 50 mg/L NaAsO2 for 12 months were assessed by western blot. Total RNA of spleen was isolated and relative mRNA levels of Foxp3, Il-10, Tnf-α, Il-6, Ifn-γ, Il-1β and Il-12 were measured by real-time PCR.ResultsOur results shown that NF-κB were continuously activated with treatment of 25 mg/L arsenic from 1, 3 to 12 months and 50 mg/L arsenic for 12 months. The transcription factor Foxp3 increased at 1 month but decreased at 3 and 12 months no matter 25 or 50 mg/L arsenic exposure. However, cytokine Il-10 always showed increased trend in mice treated with 25 or 50 mg/L arsenic for 1, 3 and 12 months. The transcriptional profiles of Tnf-α, Il-1β, Il-6, Ifn-γ and Il-12 revealed transient elevation at 1 and 3 months but shown significant decrease at 12 months on the whole. In addition, the sustained activation of inflammatory MAPK and anti-oxidative Nrf2 signaling pathways were observed in mice exposed to arsenic for 1, 3 and 12 months.ConclusionIn summary, our experiment in vivo suggested chronic arsenic exposure induces the time-dependent modulation of the inflammation and immunosuppression in spleen, which may be related to the activation of Tregs induced by MAPK/NF-κB as well as the increased transcription level of Foxp3 and Il-10.
Highlights
Arsenic contamination has become a global matter concerned
It was found that immunosuppression in arsenic-exposed people in India is related to T cell proliferation and corresponding reduction of cytokines, such as Tumor necrosis factor (TNF-α), IL-2, IL-4, IL-5, IL-10, etc
The splenic index decreased with the growth of the mice, we found no obvious changes of the size and the weight of the mice spleen, nor any other visible changes at autopsy, among the control and the arsenic treatment groups within the same durations (1, 3 and 12 months)
Summary
Studies have shown that arsenic exposure impedes cell growth and proliferation of immune function organs (spleen and thymus) [1,2,3]. A cohort study in Bangladesh has reported that exposure to arsenic during pregnancy caused the thymus gland shrank and its function impaired, leading to immunosuppression in. It has been demonstrated that arsenic could generate immunosuppressive responses by dose-dependent regulation of the NF-κB/Tregs/IL6/ STAT3 signaling axis of mouse thymus cells [5]. It was found that immunosuppression in arsenic-exposed people in India is related to T cell proliferation and corresponding reduction of cytokines, such as TNF-α (tumor necrosis factor), IL-2, IL-4, IL-5, IL-10, etc. Arsenic exposure has become a matter of worldwide concern, which is associated with immunerelated diseases. The purpose of our study was to understand the potential tuning of above responses exerted by chronic arsenic exposure
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