microRNA Expression Changes in Organotin-Driven NLRP3 Inflammasome Activation in Murine Bone Marrow Derived Macrophages

Trimethyltin (TMT) and triethyltin (TET) are two tri-organotin compounds, a group of substances reported to affect mitochondria function. These compounds were also found to activate the NLRP3 inflammasome, an inflammatory cascade that occurs in myeloid cells when primed with a Toll-like receptor ligand (i.e. LPS) followed by activation by an exogenous or endogenous danger signal. The inflammasome is a very tightly regulated mechanism, with several miRNAs playing an important role. To determine differential miRNA changes between TMT and TET induced inflammasome activation, miRNA expression profiles were evaluated in LPS-primed murine bone marrow derived macrophages (BMDMs) exposed to TMT or TET as compared to saline. mRNA expression arrays were also performed and analyzed to identify miRNA target genes in order to elucidate the key mechanism(s) by which TMT and TET activate the NLRP3 inflammasome pathway. These studies will help us understand the inflammasome regulation in macrophages by organotin. Murine bone marrow derived macrophages were exposed to LPS (33ng/ml) as a priming agent for 3 hours followed by either TMT OH (1.25 microMolar), TET (10 microMolar), or saline to induce NLRP3 inflammasome activation. Comparisons were performed between each organotin and saline. Three biological replicates for each group were set up.