Fas inhibition attenuates lipopolysaccharide-induced apoptosis and cytokine release of rat type II alveolar epithelial cells

Abstract

The aim of this study is to investigate whether silencing of Fas could have an influence on type II alveolar epithelial cell (AEC) apoptosis and inflammatory cytokine production, which prevents alveolar healing after acute lung injury (ALI). Rat primary type II AECs were isolated by elastase cell dispersion and IgG panning. The cells were transfected with Fas-specific small interfering RNA (siRNA) followed by treatment with lipopolysaccharide (LPS), Fas ligand (FasL) or both. The effects of siRNA-mediated silencing of Fas on LPS-induced apoptosis and cytokine release were then assessed. Notably, LPS, either alone or together with FasL, significantly stimulated type II AEC apoptosis and the release of tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) (P < 0.05 versus the control without treatment). Moreover, the effects exerted by both LPS and FasL were considerably counteracted by pretreatment with Fas-siRNA (P < 0.05 versus treatment with LPS and FasL). In conclusion, inhibition of Fas can diminish LPS-induced apoptosis and inflammatory cytokine production in type II AECs, and Fas specific siRNAs may have therapeutic potentials for intervention of ALI/ARDS.

SIRT1 Regulates the Human Alveolar Epithelial A549 Cell Apoptosis Induced byPseudomonas AeruginosaLipopolysaccharide

“…This study’s findings suggest that LPS can induce A549 cell apoptosis, which is consistent with previous studies [13,24,25,26]. Therefore, we hypothesize that the possible mechanisms of P. aeruginosa -induced lung damage are related to the alveolar type II epithelial cells apoptosis induced by the LPS.…”

Interaction of cyclic mechanical stretch and toll‐like receptor 4‐mediated innate immunity in rat alveolar type II cells

“…Also the concentrations of LPS (20 mg/mL) was higher and only a moderate increase of apoptotic cells (2-8%) was shown. 18 In stretched cells treated with LPS, however, an increase of apoptosis was evident. We have also shown that caspase 9, activated by the mitochondrial apoptosis pathway, is increased in these cells.…”

“…LPS has been shown to cause lung injury in rats and can induce apoptosis in lung epithelial cells. [17][18][19] However, no apoptotic effects in static cells, treated with LPS, were observed possibly due to differing experimental conditions such as a shorter time period (24 h instead of 48 h) for incubating cells and always freshly isolated ATII cells. Also the concentrations of LPS (20 mg/mL) was higher and only a moderate increase of apoptotic cells (2-8%) was shown.…”

A hypothesis for pathobiology and treatment of COVID‐19: The centrality of ACE1/ACE2 imbalance

“…Data from other in vivo models support the utility of ACEIs/AT receptor antagonists in blunting lung injury, especially of the epithelium, thus further implicating the role of Ang II in mediating these effects. Examples include acute lung injury induced by oleic acid in rats, in which the use of the ACEI captopril reduced alveolar damage/ epithelial disruption, endothelial damage and infiltration of neutrophils He et al, 2007); the protective effect of ACEI/AT receptor antagonist treatment in reducing pneumocyte death in surfactant-depleted rat lungs (Lukkarinen et al, 2005); and the efficacy of ACEIs in the treatment of radiation-induced lung injury (Medhora, Gao, Jacobs, & Moulder, 2012). This benefit has also been shown in human studies, for example, a reduction in pulmonary-related mortality by captopril administered to patients receiving total body irradiation prior to haematopoietic stem cell transplantation (Cohen et al, 2012).…”