TNF-α derived from arsenite-induced microglia activation mediated neuronal necroptosis

Arsenic, an identified environmental toxicant, poses threats to the health of human beings through contaminated water and food. Recently, increasing reports focused on arsenic-induced nerve damage, however, the underlying mechanism remains elusive. Microglia are important immune cells in the nervous system, which produce a large number of inflammatory factors including TNF-alpha when activated. Recent reports indicated that TNF-alpha is involved in the process of necroptosis, a new type of programmed cell death discovered recently. Although there were evidences suggested that arsenic could induce both microglia activation and TNF-alpha production in the nervous system, the mechanism of arsenic-induced neurotoxicity due to microglia activation is rarely studied. In addition, the role of microglia-derived TNF-alpha in response to arsenic exposure in necroptosis has not been documented before. In this study, we found that arsenite induced microglial activation through p38 MAPK signaling pathway, leading to the production of TNF-alpha. Microglia-derived TNF-alpha further induced necroptosis in the neuronal cells. Our findings suggested that necroptosis induced by microglia-derived TNF-alpha upon arsenite exposure partially played a role in arsenic-induced cell death which underlie the fundamental event of arsenic-related neurotoxicity.

Automated summary

This study investigated the mechanisms of microglia activation and TNF-alpha production induced by arsenic in the nervous system. It was found that microglia-derived TNF-alpha induced necroptosis in neuronal cells, suggesting its role in arsenic-related neurotoxicity.