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热灭活乳酸乳球菌KC24通过调节HO应激A549细胞中的NF-κB和Nrf2途径发挥抗炎和抗氧化作用。

Anti-inflammatory and antioxidative effects of heat-killed Lactococcus lactis KC24 via modulation of NF-κB and Nrf2 pathways in HO-stressed A549 cells.

作者信息

Kim Ji Hun, Baek Ji-Yeon, Kim Seo-Bin, Lee Na-Kyoung, Paik Hyun-Dong

机构信息

Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea.

Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea.

出版信息

Microb Pathog. 2025 Sep;206:107795. doi: 10.1016/j.micpath.2025.107795. Epub 2025 Jun 8.

DOI:10.1016/j.micpath.2025.107795
PMID:40494450
Abstract

Oxidative stress can contribute to various chronic diseases due to the excessive accumulation of reactive oxygen species (ROS). The lungs are particularly vulnerable to oxidative stress caused by environmental and intrinsic factors, and likely to cause asthma, chronic obstructive pulmonary disease, and lung cancer. Lactococcus lactis KC24, isolated from kimchi, has been reported to exert neuroprotective effects as a heat-killed paraprobiotic. In this study, we investigated the anti-inflammatory and antioxidant properties of heat-killed L. lactis KC24 in HO-stimulated human pulmonary epithelial cells (A549). The results showed that HO significantly reduced cell viability and increased ROS generation. However, treatment with L. lactis KC24 significantly reduced ROS levels and improved cell viability more effectively than treatment with the commercial control (Lacticaseibacillus rhamnosus GG). Quantitative real-time polymerase chain reaction and western blotting results indicated that L. lactis KC24 downregulated the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-8) and suppressed the activation of the nuclear factor-κB pathway. Furthermore, L. lactis KC24 increased the expression of nuclear factor erythroid-related factor 2 (Nrf2) and its associated antioxidant genes (heme oxygenase-1 [HO-1], NAD(P)H: quinone oxidoreductase 1, and thioredoxin reductase 1). L. lactis KC24 treatment also enhanced the transcript levels of Nrf2 and protein expression levels of HO-1. These results suggest that heat-killed L. lactis KC24 exhibits potent anti-inflammatory and antioxidant effects in HO-stressed human pulmonary epithelial cells, indicating its potential as a functional food for respiratory health management.

摘要

由于活性氧(ROS)的过度积累,氧化应激会导致各种慢性疾病。肺尤其容易受到环境和内在因素引起的氧化应激影响,可能引发哮喘、慢性阻塞性肺疾病和肺癌。从泡菜中分离出的乳酸乳球菌KC24,据报道作为一种热灭活的副益生菌具有神经保护作用。在本研究中,我们研究了热灭活的乳酸乳球菌KC24在过氧化氢(HO)刺激的人肺上皮细胞(A549)中的抗炎和抗氧化特性。结果表明,HO显著降低细胞活力并增加ROS生成。然而,与商业对照(鼠李糖乳杆菌GG)相比,乳酸乳球菌KC24处理能更有效地显著降低ROS水平并提高细胞活力。定量实时聚合酶链反应和蛋白质印迹结果表明,乳酸乳球菌KC24下调促炎细胞因子(肿瘤坏死因子-α、白细胞介素[IL]-6和IL-8)的表达,并抑制核因子-κB通路的激活。此外,乳酸乳球菌KC24增加核因子红系相关因子2(Nrf2)及其相关抗氧化基因(血红素加氧酶-1[HO-1]、NAD(P)H:醌氧化还原酶1和硫氧还蛋白还原酶1)的表达。乳酸乳球菌KC24处理还增强了Nrf2的转录水平和HO-1的蛋白表达水平。这些结果表明,热灭活的乳酸乳球菌KC24在HO应激的人肺上皮细胞中表现出强大的抗炎和抗氧化作用,表明其作为呼吸健康管理功能性食品的潜力。

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