{"title":"维生素 D 通过靶向 cathepsin D 促进自噬,从而抑制 LPS 诱导的肺损伤。","authors":"Zijuan Xu, Jinling Luan, Fengyun Wan, Meijie Zhang, Fei Ding, Ling Yang, Shuxin Dai","doi":"10.1007/s00210-024-03619-1","DOIUrl":null,"url":null,"abstract":"<p><p>Pneumonia is a frequent-occurring event in children death. Vitamin D (VD) can alleviate inflammatory response and it might be a promising adjunct to antibiotics for the treatment of acute childhood pneumonia. This study intended to uncover the relevant mechanism of VD in pneumonia. For simulating inflammatory condition, BEAS-2B cells were induced using lipopolysaccharide (LPS). Cell viability was detected using cell counting kit-8 (CCK-8) method, and cell apoptosis was detected using flow cytometry and western blot. Inflammatory cytokines as well as oxidative stress markers were detected using enzyme-linked immunosorbent assay (ELISA) and corresponding assays. Western blot evaluated the contents of cathepsin D (CTSD), apoptosis- and autophagy-related proteins. Through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot, the transfection efficiency of overexpression (OV)-CTSD was detected. Immunofluorescence assay detected light chain 3 (LC3II) level. Through SuperPred database analysis, VD can target CTSD. VD was revealed to suppress viability damage, inflammatory response, oxidative stress, and autophagy injury in BEAS-2B cells induced by LPS via targeting CTSD. However, the protective effects exhibited by VD against LPS-induced viability damage, inflammatory response, and oxidative stress in BEAS-2B cells were all counteracted by autophagy inhibitor 3-methyladenine (3-MA). Collectively, VD alleviated the severity of LPS-induced lung injury by promoting autophagy through targeting CTSD.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Vitamin D promotes autophagy to inhibit LPS-induced lung injury via targeting cathepsin D.\",\"authors\":\"Zijuan Xu, Jinling Luan, Fengyun Wan, Meijie Zhang, Fei Ding, Ling Yang, Shuxin Dai\",\"doi\":\"10.1007/s00210-024-03619-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pneumonia is a frequent-occurring event in children death. Vitamin D (VD) can alleviate inflammatory response and it might be a promising adjunct to antibiotics for the treatment of acute childhood pneumonia. This study intended to uncover the relevant mechanism of VD in pneumonia. For simulating inflammatory condition, BEAS-2B cells were induced using lipopolysaccharide (LPS). Cell viability was detected using cell counting kit-8 (CCK-8) method, and cell apoptosis was detected using flow cytometry and western blot. Inflammatory cytokines as well as oxidative stress markers were detected using enzyme-linked immunosorbent assay (ELISA) and corresponding assays. Western blot evaluated the contents of cathepsin D (CTSD), apoptosis- and autophagy-related proteins. Through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot, the transfection efficiency of overexpression (OV)-CTSD was detected. Immunofluorescence assay detected light chain 3 (LC3II) level. Through SuperPred database analysis, VD can target CTSD. VD was revealed to suppress viability damage, inflammatory response, oxidative stress, and autophagy injury in BEAS-2B cells induced by LPS via targeting CTSD. However, the protective effects exhibited by VD against LPS-induced viability damage, inflammatory response, and oxidative stress in BEAS-2B cells were all counteracted by autophagy inhibitor 3-methyladenine (3-MA). 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引用次数: 0
摘要
肺炎是儿童死亡的常见病。维生素 D(VD)可减轻炎症反应,是治疗儿童急性肺炎的抗生素辅助药物。本研究旨在揭示维生素 D 在肺炎中的相关机制。为了模拟炎症状态,研究人员使用脂多糖(LPS)诱导 BEAS-2B 细胞。用细胞计数试剂盒-8(CCK-8)法检测细胞活力,用流式细胞术和 Western 印迹法检测细胞凋亡。使用酶联免疫吸附试验(ELISA)和相应的检测方法检测炎性细胞因子和氧化应激标记物。Western 印迹评估了酪蛋白酶 D (CTSD)、凋亡和自噬相关蛋白的含量。通过实时逆转录聚合酶链反应(RT-qPCR)和 Western 印迹检测过表达(OV)-CTSD 的转染效率。免疫荧光检测了轻链 3(LC3II)的水平。通过 SuperPred 数据库分析,VD 可以靶向 CTSD。研究发现,VD能通过靶向CTSD抑制LPS诱导的BEAS-2B细胞的活力损伤、炎症反应、氧化应激和自噬损伤。然而,自噬抑制剂 3-甲基腺嘌呤(3-MA)抵消了 VD 对 LPS 诱导的 BEAS-2B 细胞活力损伤、炎症反应和氧化应激的保护作用。总之,VD 通过靶向 CTSD 促进自噬,减轻了 LPS 诱导的肺损伤的严重程度。
Vitamin D promotes autophagy to inhibit LPS-induced lung injury via targeting cathepsin D.
Pneumonia is a frequent-occurring event in children death. Vitamin D (VD) can alleviate inflammatory response and it might be a promising adjunct to antibiotics for the treatment of acute childhood pneumonia. This study intended to uncover the relevant mechanism of VD in pneumonia. For simulating inflammatory condition, BEAS-2B cells were induced using lipopolysaccharide (LPS). Cell viability was detected using cell counting kit-8 (CCK-8) method, and cell apoptosis was detected using flow cytometry and western blot. Inflammatory cytokines as well as oxidative stress markers were detected using enzyme-linked immunosorbent assay (ELISA) and corresponding assays. Western blot evaluated the contents of cathepsin D (CTSD), apoptosis- and autophagy-related proteins. Through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot, the transfection efficiency of overexpression (OV)-CTSD was detected. Immunofluorescence assay detected light chain 3 (LC3II) level. Through SuperPred database analysis, VD can target CTSD. VD was revealed to suppress viability damage, inflammatory response, oxidative stress, and autophagy injury in BEAS-2B cells induced by LPS via targeting CTSD. However, the protective effects exhibited by VD against LPS-induced viability damage, inflammatory response, and oxidative stress in BEAS-2B cells were all counteracted by autophagy inhibitor 3-methyladenine (3-MA). Collectively, VD alleviated the severity of LPS-induced lung injury by promoting autophagy through targeting CTSD.
期刊介绍:
Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.