The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Anesthesiology, Norhtern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
Int Immunopharmacol. 2019 Aug;73:312-320. doi: 10.1016/j.intimp.2019.04.035. Epub 2019 May 23.
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.
脂多糖(LPS)腹腔注射可诱导进行性肺损伤和肺部炎症。白细胞介素-1β(IL-1β)是一种关键的促炎细胞因子,可通过 NALP3 炎性体进一步加剧炎症反应。虽然核受体 Rev-erbα 可降低 LPS 诱导的肺部炎症水平,但具体机制尚不清楚。在本研究中,我们研究了 LPS 诱导的 IL-1β和 Rev-erbα产生对肺部炎症发展的影响。研究表明,Rev-erbα可降低 LPS 腹腔注射后 IL-1β的产生和肺损伤,这依赖于 NF-κB/NALP3 途径。因此,Rev-erbα可通过调节 IL-1β的产生来减轻急性肺损伤的程度。该机制可能为肺损伤提供一种新的潜在治疗方法。