The role of NALP3 in mediating noninfectious ALI has been revealed by two recent studies. Gasse and colleagues reported that uric acid locally produced in the lung upon bleomycin (BLM)-induced DNA damage and degradation triggers NALP3 inflammasome activation, and in turn causes lung injury (146) . Reduction of uric acid levels using the inhibitor of uric acid synthesis allopurinol or uricase leads to a decrease in BLM-induced IL-1β production, lung inflammation, repair and fibrosis. Local administration of exogenous uric acid crystals recapitulates lung inflammation and repair, which depend on the NALP3 inflammasome, MyD88 and IL-1R1 pathways and TLR2 and TLR4 for optimal inflammation but are independent of the IL-18 receptor (146) . Babelova et al., however, reported the role of biglycan, a ubiquitous LRR proteoglycan of the extracellular matrix, in mediating ALI through interacting with TLR2 and TLR4 on macrophages (147) . The study showed that in macrophages soluble biglycan induces the NLRP3/ASC inflammasome and subsequent activation of caspase-1 and release of mature IL-1β without need for additional costimulatory factors. This is caused by the interaction of biglycan with TLR2/4 and purinergic P2 × 4/P2 × 7 receptors, which induces receptor cooperativity. Furthermore, ROS formation is involved in biglycan-mediated activation of the inflammasome. By signaling through TLR2/4 biglycan stimulates the expression of NLRP3 and pro-IL-1β mRNA. These results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and suggest a fundamental paradigm of how tissue stress and injury are monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response (147) .