AIM2 inflammasome mediates Arsenic-induced secretion of IL-1 ß and IL-18.

ABSTRACT

Chronic sterile inflammation has been implicated in the pathogenesis of many cancers, including skin cancer. Chronic arsenic exposure is closely associated with the development of skin cancer. However, there is a lack of understanding how arsenic induces chronic inflammation in the skin. Interleukin-1 family cytokines play a central role in regulating immune and inflammatory response. IL-1α, IL-1ß and IL-18 are three pro-inflammatory cytokines in IL-1 family. Their secretion, especially the secretion of IL-1ß and IL-18, is regulated by inflammasomes which are multi-protein complexes containing sensor proteins, adaptor protein and caspase-1. The data from current study show sub-chronic arsenic exposure activates AIM2 inflammasome which in turn activates caspase-1 and enhances the secretion of IL-1ß and IL-18 in HaCaT cells and the skin of BALB/c mice. In addition, arsenic-promoted activation of AIM2 inflammasome and increase of IL-1ß/IL-18 production are inhibited by PKR inhibitor in HaCaT cells or in the skin of PKR mutant mice, indicating a potential role of PKR in arsenic-induced sterile inflammation.