Fig. 10

Schematic illustration of the ROS/PARP/TRPM2 signaling pathway that mediates SiNPs-induced pulmonary inflammation in mice. SiNPs are ingested through intratracheal exposure and, upon endocytosis into bronchial epithelial cells, induce ROS production, which activates the TRPM2 channel through the PARP-mediated generation of ADPR in the nucleus. TRPM2 channel activation in turn increases intracellular zinc and calcium ions to impair the degradation function of lysosomes. Lysosomal dysfunction blocks autophagic flux that triggers inflammation by generating cytokines, IL-1β and IL-6, and also chemokines, CXCL-1 and CXCL-8, which are critical for neutrophil recruitment