Programmed cell death‑1/programmed cell death‑ligand 1 inhibitors exert antiapoptosis and antiinflammatory activity in lipopolysaccharide stimulated murine alveolar macrophages

Jia, Lingling; Liu, Kai; Teng, Fei; Liu, Qian; Zhao, Xiwei; Hou, Linyi; Zhang, Wenkai

doi:10.3892/etm.2021.9831

Cited by 7 publications

(3 citation statements)

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“…On one hand, activation of PD-1 signaling mitigates hepatic I/R injury by inhibiting T cell activation and Kupffer cell/macrophage function [ 33 ]; on the other hand, high PD-1 expression in cardiomyocytes after I/R results in inflammatory injury to myocardial tissues following reperfusion [ 13 ]. Downregulation of the PD-1/PD-L1 signal axis inhibits the apoptosis of AMs, reduces the secretion of inflammatory factors, and enhances lung protection in a mouse model of acute lung injury [ 34 ]. Our results support a more detrimental role for PD-1 expression after lung I/R, as inhibition of PD-1 with BMS202 significantly reduced inflammation and improved lung tissue and cell damage.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

Jingyuan

Zhao

et al. 2022

Inflammation

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Polarization of alveolar macrophages (AMs) into the M1 phenotype contributes to inflammatory responses and tissue damage that occur during lung ischemia–reperfusion injury (LIRI). Programmed cell death factor-1 (PD-1) regulates polarization of macrophages, but its role in LIRI is unknown. We examined the role of PD-1 in AM polarization in models of LIRI in vivo and in vitro. Adult Sprague–Dawley rats were subjected to ischemia–reperfusion with or without pretreatment with a PD-1 inhibitor, SHP1/2 inhibitor, or Akt activator. Lung tissue damage and infiltration by M1-type AMs were assessed. As an in vitro complement to the animal studies, rat alveolar macrophages in culture were subjected to oxygen/glucose deprivation and reoxygenation. Levels of SHP1/2 and Akt proteins were evaluated using Western blots, while levels of pro-inflammatory cytokines were measured using enzyme-linked immunosorbent assays. Injury upregulated PD-1 both in vivo and in vitro. Inhibiting PD-1 reduced the number of M1-type AMs, expression of SHP1 and SHP2, and levels of inflammatory cytokines. At the same time, it partially restored Akt activation. Similar results were observed after inhibition of SHP1/2 or activation of the PI3K/Akt pathway. PD-1 promotes polarization of AMs to the M1 phenotype and inflammatory responses through the SHP1/2-PI3K/Akt axis. Inhibiting PD-1 may be an effective therapeutic strategy to limit LIRI.

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Section: Resultsmentioning

confidence: 99%

Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

Jingyuan

Zhao

et al. 2022

Inflammation

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Section: Role Of Pd-l1-mediated Intracellular Signaling In Sepsis-ind...mentioning

confidence: 99%

“…Additionally, the number of PD-1 + cells in the lungs of human newborns with intrauterine infection was prominently higher than those who died from non-infectious causes (129). Therefore, PD-1 plays a pivotal role in the mechanism of sepsis-induced lung injury, and PD-1/PD-L1 inhibitors may be potential therapeutic targets (130). Alfred Ayala et al constructed a mouse model of sepsisinduced lung injury using septic aggression-induced sepsis after hemorrhagic shock (Hem-CLP) and found that PD-L1 expression was significantly upregulated on vascular endothelial cells (ECs) or lung epithelial cells (EpiCs) in mice with indirect acute lung injury (iALI) 24 hours after sepsis injury (131).…”

Section: Lungmentioning

confidence: 99%

The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways

Chen,

Guo,

Zhu

et al. 2023

Front. Immunol.

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Sepsis currently remains a major contributor to mortality in the intensive care unit (ICU), with 48.9 million cases reported globally and a mortality rate of 22.5% in 2017, accounting for almost 20% of all-cause mortality worldwide. This highlights the urgent need to improve the understanding and treatment of this condition. Sepsis is now recognized as a dysregulation of the host immune response to infection, characterized by an excessive inflammatory response and immune paralysis. This dysregulation leads to secondary infections, multiple organ dysfunction syndrome (MODS), and ultimately death. PD-L1, a co-inhibitory molecule expressed in immune cells, has emerged as a critical factor in sepsis. Numerous studies have found a significant association between the expression of PD-1/PD-L1 and sepsis, with a particular focus on PD-L1 expressed on neutrophils recently. This review explores the role of PD-1/PD-L1 in immunostimulatory and anti-inflammatory pathways, illustrates the intricate link between PD-1/PD-L1 and sepsis, and summarizes current therapeutic approaches against PD-1/PD-L1 in the treatment and prognosis of sepsis in preclinical and clinical studies.

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PD-L1 Expression Is Increased in LPS-Induced Acute Respiratory Distress Syndrome by PI3K-AKT-Egr-1/C/EBPδ Signaling Pathway

Yan,

Chen,

Wang

et al. 2024

Inflammation

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Programmed cell death‑1/programmed cell death‑ligand 1 inhibitors exert antiapoptosis and antiinflammatory activity in lipopolysaccharide stimulated murine alveolar macrophages

Cited by 7 publications

References 0 publications

Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways

PD-L1 Expression Is Increased in LPS-Induced Acute Respiratory Distress Syndrome by PI3K-AKT-Egr-1/C/EBPδ Signaling Pathway

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