The effect of lipoxin A4 on lipopolysaccharide-induced inflammatory responses in airway epithelial cells
10.3969/j.issn.1673-9701.2025.06.008
- VernacularTitle:脂氧素A4对脂多糖诱导气道上皮细胞炎症反应的影响
- Author:
Zhenjie WU
1
Author Information
1. 浙江省台州医院呼吸与危重症医学科,浙江台州 317000
- Publication Type:Journal Article
- Keywords:
Lipoxins;
Lipopolysaccharide;
Airway epithelial cells;
Inflammation
- From:
China Modern Doctor
2025;63(6):40-44
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of lipoxin A4(LXA4)on the inflammatory response in airway epithelial cells induced by lipopolysaccharide(LPS),and to further explore its underlying mechanism of action.Methods An in vitro inflammation model was established by stimulating normal human bronchial epithelial cells(BEAS-2B)with LPS.BEAS-2B cells were divided into four groups.Control group:No treatment was applied;LPS group:BEAS-2B cells were incubated with 100 ng/ml LPS for 24 hours.LXA4 group:BEAS-2B cells were pretreated with 100 nmol/L LXA4 for 30 minutes.LPS+LXA4 group:BEAS-2B cells were pretreated with 100 nmol/L LXA4 for 30 minutes in culture medium and then incubated with 100 ng/ml LPS for an additional 24 hours.Cell viability assays were conducted to assess the cytotoxicity of LXA4.Enzyme linked immunosorbent assay was used to measure the concentrations of interleukin(IL)-6,IL-8,and tumor necrosis factor-α(TNF-α)in the cell culture supernatants.Western blot analysis was employed to detect the expression of matrix metalloproteinase-9(MMP-9)protein in the cells.Finally,Western blot analysis was performed to examine the expression of proteins related to the nuclear factor-KB(NF-κB)signaling pathway.Results ①LXA4 exhibited negligible cytotoxicity towards BEAS-2B cells at concentrations below 100 nmol/L.Relative to control group,the exposure of BEAS-2B cells to 100ng/ml of LPS for a period of 24 hours led to a substantial augmentation in the levels of IL-6,IL-8,and TNF-α within the cellular supernatants(P＜0.01).Pretreatment with 100 nmol/L LXA4 for a period of 30 minutes markedly attenuated the levels of IL-6,IL-8,and TNF-α in LPS-stimulated BEAS-2B cells(P＜0.05).②Compared with control group,the expression of MMP-9 protein was significantly increased in LPS group(P＜0.01).When compared to LPS group,the expression of MMP-9 protein was significantly decreased in LPS+LXA4 group(P＜0.05).③The expression of p65 within the cytoplasm of BEAS-2B cells exhibited a notable decline as the duration of LPS stimulation was extended.Specifically,stimulation of BEAS-2B cells with 100 ng/ml LPS induced the degradation of inhibitor of κB-α(IκB-α),with the most pronounced effect observed at 30 minutes.Following a 30-minute pretreatment with 100 nmol/L LXA4,there was a significant reduction in both IκB-α expression and cytoplasmic NF-κB p65 levels,yielding statistical significance(P＜0.05).Conclusion LXA4 exerts inhibitory effects on the production of inflammatory mediators,including IL-6,IL-8,and TNF-α,as well as the expression of MMP-9 in LPS-stimulated airway epithelial cells.The underlying mechanism may involve the suppression of NF-κB signaling pathway.
