Exp Ther Med. 2021 Apr;21(4):400. doi: 10.3892/etm.2021.9831. Epub 2021 Feb 24.
ABSTRACT
Acute lung injury caused by sepsis remains one of the most difficult challenges faced by patients in intensive care units and is associated with a high mortality rate. The aim of the present study was to investigate whether programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) inhibitors reduce alveolar macrophage apoptosis, reduce inflammatory factor release and relieve inflammation. For this purpose, murine alveolar macrophages, MH-S, were cultured and divided into control, lipopolysaccharide (LPS) and LPS+BMS-1 (PD-1/PD-L1 inhibitors) groups. LPS (10 ng/ml) was added to the LPS and LPS+BMS-1 groups for 24 h and PD-1/PD-L1 inhibitor BMS-1 (1 µmol/l) was added to the LPS+BMS-1 group for 72 h. PD-1 mRNA expression was detected using reverse transcription-quantitative PCR and PD-1 protein expression was detected using western blotting in the control, LPS and LPS+BMS-1 groups of macrophages. MH-S apoptosis was detected using flow cytometry with Annexin V/PI staining. The levels of the inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and IL-10 were detected by ELISA. Murine alveolar macrophages expressed PD-1 at both the molecular and protein levels and PD-1 expression was increased in MH-S cells stimulated with LPS. Compared with the LPS group, the expression of PD-1 in the LPS+BMS-1 group was significantly decreased. Flow cytometry demonstrated that there was increased apoptosis of alveolar macrophages in the LPS group compared with the control group, whereas, alveolar macrophages notably decreased apoptosis in the LPS+BMS-1 group compared with the LPS group. There was no statistical difference between the control group and the LPS+BMS-1 group. IL-1β, IL-6, TNF-α and IL-10 were increased in the LPS group compared with the control group. The levels of IL-1β, IL-6 and TNF-α in th e LPS+BMS-1 group were lower compared with those in the LPS group whereas IL-10 was further increased. In vitro, the PD-1/PD-L1 inhibitor, BMS-1, decreases alveolar macrophage apoptosis compared with the LPS group to maintain effective immune clearance and reduce inflammatory factor release. This decreased the inflammatory response and reduced acute lung injury caused by sepsis. Therefore, PD-1/PD-L1 inhibitors may be a potential therapeutic target for acute lung injury in patients with sepsis.
PMID:33680122 | PMC:PMC7918472 | DOI:10.3892/etm.2021.9831
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