{"title":"DEPTOR alleviates LPS-induced inflammation and ER stress in WI-38 cells.","authors":"Xiangxiang Shi, Jin Ding, Bihe Zeng","doi":"10.15586/aei.v53i4.1380","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>WI-38 human fetal lung fibroblast cells were employed to establish an <i>in vitro</i> 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 <i>kappa B</i> signaling was comprehensively evaluated using quantitative real-time polymerase chain reaction, Western blot analysis, enzyme-linked-immunosorbent serologic assay, flow cytometry, and biochemical assays.</p><p><strong>Results: </strong>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 <i>glutathione</i> levels (P < 0.01)-and inhibits apoptosis, reducing apoptotic cell percentages by over 10% (P < 0.01).</p><p><strong>Conclusion: </strong>These results suggest that DEPTOR confers a protective role against LPS-induced cellular injury, supporting its potential as a promising therapeutic target for mitigating.</p>","PeriodicalId":7536,"journal":{"name":"Allergologia et immunopathologia","volume":"53 4","pages":"60-67"},"PeriodicalIF":2.1000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergologia et immunopathologia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.15586/aei.v53i4.1380","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ALLERGY","Score":null,"Total":0}
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.
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.