sr-8278 and Acute-Lung-Injury

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.

Topics: Acute Lung Injury; Animals; Glycine; Interleukin-1beta; Isoquinolines; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred C57BL; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Nuclear Receptor Subfamily 1, Group D, Member 1; RAW 264.7 Cells; Signal Transduction; Thiophenes