DEPTOR alleviates LPS-induced inflammation and ER stress in WI-38 cells.

IF 2.1 4区 医学 Q3 ALLERGY
Allergologia et immunopathologia Pub Date : 2025-07-01 eCollection Date: 2025-01-01 DOI:10.15586/aei.v53i4.1380
Xiangxiang Shi, Jin Ding, Bihe Zeng
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引用次数: 0

Abstract

Background: Pediatric pneumonia is a severe inflammatory condition frequently precipitated by bacterial endotoxins, such as lipopolysaccharide (LPS), which can elicit oxidative stress, endoplasmic reticulum (ER) stress, and apoptotic cell death. DEP domain-containing mTOR-interacting protein (DEPTOR), an endogenous inhibitor of mTOR signaling, has been implicated in the regulation of inflammation and ER homeostasis. However, its specific function in the pathogenesis of pneumonia remains poorly defined.

Methods: WI-38 human fetal lung fibroblast cells were employed to establish an in vitro model of LPS-induced inflammation. DEPTOR was overexpressed via plasmid transfection to examine its functional role. The impact of DEPTOR on pro-inflammatory cytokine release, oxidative and ER stress responses, apoptosis, and nuclear factor kappa B signaling was comprehensively evaluated using quantitative real-time polymerase chain reaction, Western blot analysis, enzyme-linked-immunosorbent serologic assay, flow cytometry, and biochemical assays.

Results: DEPTOR expression is significantly downregulated in LPS-stimulated WI-38 cells (P < 0.01). DEPTOR overexpression markedly suppresses LPS-induced pro-inflammatory cytokine production (P < 0.01), ameliorates oxidative and ER stress-as indicated by decreased lipid peroxidation and restoration of superoxide dismutase and glutathione levels (P < 0.01)-and inhibits apoptosis, reducing apoptotic cell percentages by over 10% (P < 0.01).

Conclusion: These results suggest that DEPTOR confers a protective role against LPS-induced cellular injury, supporting its potential as a promising therapeutic target for mitigating.

DEPTOR可减轻lps诱导的WI-38细胞炎症和内质网应激。
背景:儿童肺炎是一种严重的炎症性疾病,通常由细菌内毒素如脂多糖(LPS)引起,可引起氧化应激、内质网应激和细胞凋亡。DEP结构域含有mTOR相互作用蛋白(DEPTOR),一种内源性mTOR信号抑制剂,参与炎症和内质网稳态的调节。然而,其在肺炎发病机制中的具体功能仍不清楚。方法:采用WI-38人胎肺成纤维细胞建立脂多糖诱导的体外炎症模型。通过质粒转染过表达DEPTOR来检测其功能作用。通过定量实时聚合酶链反应、Western blot分析、酶联免疫吸附血清学分析、流式细胞术和生化分析,全面评估DEPTOR对促炎细胞因子释放、氧化和内质网应激反应、细胞凋亡和核因子κ B信号传导的影响。结果:lps刺激的WI-38细胞中,DEPTOR表达明显下调(P < 0.01)。DEPTOR过表达可显著抑制lps诱导的促炎细胞因子的产生(P < 0.01),改善氧化应激和内质肽应激(P < 0.01),通过降低脂质过氧化和恢复超氧化物歧化酶和谷胱甘肽水平(P < 0.01),抑制凋亡,使凋亡细胞百分比降低10%以上(P < 0.01)。结论:这些结果表明,DEPTOR对lps诱导的细胞损伤具有保护作用,支持其作为有希望的治疗靶点的潜力。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
131
审稿时长
6-12 weeks
期刊介绍: Founded in 1972 by Professor A. Oehling, Allergologia et Immunopathologia is a forum for those working in the field of pediatric asthma, allergy and immunology. Manuscripts related to clinical, epidemiological and experimental allergy and immunopathology related to childhood will be considered for publication. Allergologia et Immunopathologia is the official journal of the Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) and also of the Latin American Society of Immunodeficiencies (LASID). It has and independent international Editorial Committee which submits received papers for peer-reviewing by international experts. The journal accepts original and review articles from all over the world, together with consensus statements from the aforementioned societies. Occasionally, the opinion of an expert on a burning topic is published in the "Point of View" section. Letters to the Editor on previously published papers are welcomed. Allergologia et Immunopathologia publishes 6 issues per year and is included in the major databases such as Pubmed, Scopus, Web of Knowledge, etc.
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