NLRP3 inflammasomes are required for MUC5AC expression induced by S100A8, S100A9 and S100A12

Abstract

Abstract S100A8, S100A9, and S100A12, damage-associated molecular pattern (DAMP) molecules, initiate and modulate local inflammation and innate immune responses. NLRP3 is a component of the innate immune system that detects danger signals. Activation of NLRP3 is known to be associated with the pathogenesis of pulmonary obstructive diseases such as asthma and COPD. We have previously demonstrated that these three S100 proteins are able to induce MUC5AC production in airway epithelial cells through activation of NF-kB and ERK pathways. In this study, we examine the involvement of NLRP3 inflammasomes in the S100 proteins-induced MUC5AC production. Treatment of NCI-H292 cells with the S100 proteins results in synthesis of NLRP3 mRNA and protein along with increased procaspase-1 and IL-1b secretion. Introduction of NLRP3 siRNA leads to a decrease in MUC5AC expression, which is also accompanied by diminished IL-1b mRNA. In addition, NLRP3 siRNA inhibits S100A12-induced activation of NF-kB. In line, MCC950, an inhibitor of NLRP3 inflammasome oligomerization, abolishes MUC5AC production, with no effect on synthesis of NLRP3 molecule. Collectively, these data suggest that NLRP3 inflammasome plays an active role in S100 protein-induced mucin production in airway epithelial cells.