Rev-erbα can regulate the NF-κB/NALP3 pathway to modulate lipopolysaccharide-induced acute lung injury and inflammation

• Published in: International immunopharmacology 2019-08, Vol.73, p.312-320
• Main Authors: Yu, Dapeng, Fang, Xiangzhi, Xu, Yingying, Xiao, Huashi, Huang, Tianfeng, Zhang, Yang, Ge, Yali, Li, Yong, Zong, Liang, Gao, Ju
• Format: Article
• Language: English
• Subjects: Acute lung injury (ALI); Acute Lung Injury - chemically induced; Acute Lung Injury - immunology; Acute Lung Injury - pathology; Animals; Glycine - analogs & derivatives; Glycine - pharmacology; IL-1β; Inflammasomes; Inflammation; Injection; Injury prevention; Interleukin-1beta - immunology; Interleukins; Isoquinolines - pharmacology; Lipopolysaccharide (LPS); Lipopolysaccharides; Lung - drug effects; Lung - metabolism; Lung - pathology; Lungs; Male; Mice; Mice, Inbred C57BL; NALP3 inflammasome; NF-kappa B - immunology; NF-κB protein; Nitric oxide; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; Nuclear factor-kappa B (NF-κB); Nuclear Receptor Subfamily 1, Group D, Member 1 - agonists; Nuclear Receptor Subfamily 1, Group D, Member 1 - antagonists & inhibitors; Nuclear Receptor Subfamily 1, Group D, Member 1 - immunology; RAW 264.7 Cells; Rev-erbα; Signal Transduction; Thiophenes - pharmacology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.04.035

Progressive lung injury and pulmonary inflammation can be induced by an intraperitoneal injection of lipopolysaccharide (LPS). Interleukin-1β (IL-1β) is a key pro-inflammatory cytokine that can further exaggerate inflammation, which is cleaved and activated by the NALP3 inflammasome. Although the nuclear receptor Rev-erbα attenuates the level of LPS-induced pulmonary inflammation, the mechanism remains unclear. In this study, we investigated the influence of LPS-induced production of IL-1β and Rev-erbα on the development of lung inflammation. Herein, we demonstrate that Rev-erbα reduces IL-1β production and lung injury following an intraperitoneal injection of LPS, which is dependent on the NF-κB/NALP3 pathway. Thus, Rev-erbα is able to decrease the extent of acute lung injury by regulating IL-1β production. This mechanism may represent a potential novel therapeutic approach for lung injury. •We firstly demonstrate that Rev-erbα inhibit IL-1β production to reduce lung injury through NF-κB/NALP3 pathway in mice model. Thus, Rev-erbα might be a good target to decrease the extent of acute lung injury. This mechanism may represent a potential novel therapeutic approach for lung injury.