Suppression of NLRP3 inflammasome pathway improves acute lung injury

NLRP3 inflammasome is a pathway stimulated by a different cellular insults to activate innate immune defenses via the activation of Caspase-1 and several of pro-inflammatory cytokines, such as IL-1β and IL-18. NLRP3 expression is increased in numerous human inflammatory diseases, including pulmonary diseases. Pleural injection of carrageenan caused an acute inflammatory response, characterized by tissue damage, leukocyte infiltration, inflammatory exudates and increased myeloperoxidase activity. The aim of this study was to investigate the effect of the administration of two different inflammasome blocking agents BAY 11-7082 (30 mg/kg, i.p.) and Brilliant Blue G (BBG) (45.5 mg/kg, i.p.) in a mouse model of carrageenan-induced pleurisy. BAY 11-7082 or BBG administration 1 h after carrageenan injection reduced pulmonary membrane thickening and polymorphonuclear leukocyte infiltration, decreased NF-kB translocation in the nucleus the assembly of the NLRP3 inflammasome complex. Moreover ,they down-regulated iNOS, nitrotyrosine, and poly-ADP-ribosyl polymerase expression and repressed carrageenan-induced apoptosis. The results demonstrate that inflammasome-blocking agents administration can reduce the development of acute carrageenan-induced lung injury