Assessing the Effects of Inorganic Arsenic on IL-1β and TNFα Secretion, Gene Expression, and DNA Methylation in Murine Macrophages to Gauge Immunotoxic Effects

Abstract

I plan to investigate whether or not genes for the NLRP3 inflammasome or TACE (Adam 17) are indeed differentially regulated in M1 macrophages exposed to arsenite. If these genes are differentially expressed, I will have insight to future steps of analysis that may reveal the mechanism by which the toxicants influence this process. This study hypothesizes that treatment of murine macrophages in vitro at nanomolar concentrations of arsenite will create cytotoxic or sub-cytotoxic conditions that induce increased secretion of inflammatory cytokine IL-1B and TNFa. Furthermore, an increase in IL-1B secretion will be coupled with an upregulation of genes involved in the formation of the NLRP3 inflammasome, and an increase in TNFa secretion will be coupled with an upregulation of genes involved with TACE (Adam17). Results that reveal the mechanism by which arsenite poisoning or public health measures related to low dose arsenite-induced immune dysfunction.