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L通过降低NF-κB和NLRP3炎性小体信号传导减轻人A-549细胞中的急性肺损伤。

L. alleviates acute lung injury in human A-549 cells by reducing NF-κB and NLRP3 inflammasome signaling.

作者信息

Hsieh Lan-Chi, Hsieh Shu-Ling, Ping Tsu-Ni, Huang Yi-Chun, Lin Ssu-Jung, Chi Hsing-Yu, Wu Chih-Chung

机构信息

Department of Dietetics, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan, R.O.C.

Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan, R.O.C.

出版信息

Pharm Biol. 2025 Dec;63(1):1-13. doi: 10.1080/13880209.2024.2433994. Epub 2024 Dec 13.

Abstract

BACKGROUND

L. (celery) is a dietary vegetable with anti-inflammatory properties. It has the potential to treat acute lung injury (ALI) caused by COVID-19 or other diseases.

OBJECTIVE

To investigate the effects of water extract (AGWE) on ALI in human lung A-549 cells induced by lipopolysaccharide (LPS).

MATERIALS AND METHODS

A-549 cells were treated with AGWE for 24 h and then stimulated with 10 μg/mL LPS for another 24 h. The effects of AGWE on cell viability, the inflammatory response, oxidative stress, and apoptosis and their regulatory factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling activation were analyzed.

RESULTS

Treatment with 5-50 μg/mL AGWE reversed the decrease in cell viability caused by LPS ( < 0.05). AGWE can reduce interleukin (IL)-1β, IL-6, IL-18, and TNF-α levels; their EC values are 61.4, 65.7, 37.8, and 79.7 μg/mL, respectively. AGWE can reduce reactive oxygen species and thiobarbituric acid reactive substances in A-549 cells induced by LPS. AGWE also reduced the levels of apoptosis (EC50 of 74.8 μg/mL) and its regulators (Bid; Caspase-9, -8, and -3; Bax) and increased the levels of the mitochondrial membrane potential in A-549 cells induced by LPS. AGWE can also decrease the protein levels of NLRP3 and Caspase-1 and the activation of NF-κB signaling in A-549 cells induced by LPS.

CONCLUSIONS

These results show that 10 and 50 μg/mL AGWE can reduce the acute inflammation induced by LPS by reducing NF-κB and NLRP3 inflammasome signaling and mitochondria-dependent apoptosis pathways.

摘要

背景

芹菜是一种具有抗炎特性的食用蔬菜。它具有治疗由新型冠状病毒肺炎或其他疾病引起的急性肺损伤(ALI)的潜力。

目的

研究水提取物(AGWE)对脂多糖(LPS)诱导的人肺A-549细胞急性肺损伤的影响。

材料与方法

用AGWE处理A-549细胞24小时,然后用10μg/mL LPS再刺激24小时。分析AGWE对细胞活力、炎症反应、氧化应激、细胞凋亡及其调节因子、活化B细胞核因子κB(NF-κB)和含NLR家族pyrin结构域3(NLRP3)炎性小体信号激活的影响。

结果

用5-50μg/mL AGWE处理可逆转LPS引起的细胞活力下降(P<0.05)。AGWE可降低白细胞介素(IL)-1β、IL-6、IL-18和肿瘤坏死因子-α水平;它们的半数有效浓度分别为61.4、65.7、37.8和79.7μg/mL。AGWE可降低LPS诱导的A-549细胞中的活性氧和硫代巴比妥酸反应性物质。AGWE还降低了LPS诱导的A-549细胞中的细胞凋亡水平(半数有效浓度为74.8μg/mL)及其调节因子(Bid;半胱天冬酶-9、-8和-3;Bax),并提高了线粒体膜电位水平。AGWE还可降低LPS诱导的A-549细胞中NLRP3和半胱天冬酶-1的蛋白水平以及NF-κB信号的激活。

结论

这些结果表明,10和50μg/mL AGWE可通过降低NF-κB和NLRP3炎性小体信号以及线粒体依赖性细胞凋亡途径来减轻LPS诱导的急性炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3696/11648134/f673d41da5f8/IPHB_A_2433994_F0001_C.jpg

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