title: AIM2 inflammasome mediates Arsenic-induced secretion of IL-1 β 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-1β and IL-18 are three pro-inflammatory cytokines in IL-1 family. Their secretion, especially the secretion of IL-1β 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-1β 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-1β/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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University , Fuzhou, Fujian, China.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University , Fuzhou, Fujian, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine , Lexington, KY, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biochemistry, College of Medicine, Yichun University , Yichun, Jiangxi, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Graduate Center for Toxicology, University of Kentucky College of Medicine , Lexington, KY, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine , Lexington, KY, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Frank
authors.affiliation: The First Affiliated Hospital of Xiamen University , Xiamen, Fujian, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA; Department of Neurology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine , Lexington, KY, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
keywords: Arsenic; cancer; cytokine; inflammation; skin