Release of IL-1βTriggered by Milan Summer PM10: Molecular Pathways Involved in the Cytokine Release

Abstract

Particulate matter (PM) exposure is related to pulmonary and cardiovascular diseases, with increased inflammatory status. The release of the proinflammatory interleukin- (IL-) 1β, is controlled by a dual pathway, the formation of inactive pro-IL-1β, through Toll-like receptors (TLRs) activation, and its cleavage by NLRP3 inflammasome. THP-1-derived macrophages were exposed for 6 h to 2.5 μg/cm2of Milan PM10, and the potential to promote IL-1βrelease by binding TLRs and activating NLRP3 has been examined. Summer PM10, induced a marked IL-1βresponse in the absence of LPS priming (50-fold increase compared to unexposed cells), which was reduced by caspase-1 inhibition (91% of inhibition respect summer PM10-treated cells) and by TLR-2 and TLR-4 inhibitors (66% and 53% of inhibition, resp.). Furthermore, summer PM10increased the number of early endosomes, and oxidative stress inhibition nearly abolished PM10-induced IL-1βresponse (90% of inhibition). These findings suggest that summer PM10contains constituents both related to the activation of membrane TLRs and activation of the inflammasome NLPR3 and that TLRs activation is of pivotal importance for the magnitude of the response. ROS formation seems important for PM10-induced IL-1βresponse, but further investigations are needed to elucidate the molecular pathway by which this effect is mediated.