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REV-ERBα 可以调节 NF-κB/NALP3 通路,从而调节脂多糖诱导的急性肺损伤和炎症。

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

机构信息

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.

出版信息

Int Immunopharmacol. 2019 Aug;73:312-320. doi: 10.1016/j.intimp.2019.04.035. Epub 2019 May 23.

Abstract

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.

摘要

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。

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