Chronic arsenic exposure induces the time-dependent modulation of inflammation and immunosuppression in spleen

Abstract

Background: Arsenic 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. Methods: Kunming 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. Results: Our 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-γand 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. Conclusion: In 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.