Journal
JOURNAL OF PINEAL RESEARCH
Volume 60, Issue 4, Pages 405-414Publisher
WILEY
DOI: 10.1111/jpi.12322
Keywords
acute lung injury; histone; melatonin; NLRP inflammasome; reactive oxygen species
Categories
Funding
- National Science and Technology Major Project [2013ZX10004608, 2012AA020601]
- Natural Science Foundation of China [NSFC31071316, NSFC81261130024]
- Ministry of Science/Technology [2009CB941701]
- CAU Scientific Fund [2012YJ034]
- National Undergraduate Training Programs for Innovation and Entrepreneurship [201510019048]
- Project for Extramural Scientists of State Key Laboratory of Agrobiotechnology [2015SKLAB6-13]
Ask authors/readers for more resources
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 well-known 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-1 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available