|Yong Zhang, Xiru Li, Jamison J. Grailer, Na Wang, George F. Gao, Peter A. Ward, Dun-Xian Tan and Xiangdong Li. Melatonin alleviates acute lung injury through inhibiting the NLRP3 inﬂammasome. J. Pineal Res. DOI:10.1111/jpi.12322|
Melatonin alleviates acute lung injury through inhibiting the NLRP3 inﬂammasome
Yong Zhang, Xiru Li, Jamison J. Grailer, Na Wang, Mingming Wang, Jianfei Yao, Rui Zhong, George F. Gao, Peter A. Ward, Dun-Xian Tan and Xiangdong Li
J. Pineal Res
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders, and there are currently no Food and Drug Administration–approved drug therapies. Melatonin is a wellknown anti-inﬂammatory molecule, which has proven to be eﬀective in ALI induced by many conditions. Emerging studies suggest that the NLRP3 inﬂammasome plays a critical role during ALI. How melatonin directly blocks activation of the NLRP3 inﬂammasome in ALI remains unclear. In this study, using an LPS-induced ALI mouse model, we found intratracheal (i.t.) administration of melatonin markedly reduced the pulmonary injury and decreased the inﬁltration of macrophages and neutrophils into lung. During ALI, the NLRP3 inﬂammasome is signiﬁcantly activated with a large amount of IL-1b and the activated caspase-1 occurring in the lung. Melatonin inhibits the activation of the NLRP3 inﬂammasome by both suppressing the release of extracellular histones and directly blocking histone-induced NLRP3 inﬂammasome activation. Notably, i.t. route of melatonin administration opens a more eﬃcient therapeutic approach for treating ALI.