Haizhen Jin, Shuangxia Dong, Zhihui Li, Dai Xinjian
{"title":"敲低ARHGDIB可通过PRKACB/NF-κB途径促进lps诱导的肺泡上皮细胞自噬并减轻炎症。","authors":"Haizhen Jin, Shuangxia Dong, Zhihui Li, Dai Xinjian","doi":"10.15586/aei.v53i5.1362","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is a critical clinical condition with high mortality, necessitating the development of more effective therapeutic strategies. Rho Guanine nucleotide dissociation inhibitor (GDP) beta (ARHGDIB) has been shown to exert protective effects against noxious stimuli in various disease models.</p><p><strong>Objective: </strong>In this study, we investigated whether ARHGDIB knockdown had a protective effect on lipopolysaccharide (LPS)-induced injury in alveolar epithelial cells and elucidated its underlying molecular mechanisms.</p><p><strong>Material and methods: </strong>Mouse alveolar epithelial cells that were isolated from the lung of a 5-month-old female mouse (MLE-12) were treated with LPS, followed by ARHGDIB knockdown and overexpression of protein kinase A (PKA)-activated catalytic subunit β (PRKACB). Oxidative stress and apoptosis were assessed, while inflammatory cytokine levels were quantified using enzyme-linked immunosorbent serologic assays. Autophagy and PRKACB/nuclear factor <i>kappa B</i> (NF-κB) pathway activation was evaluated by Western blot analysis. Results: LPS upregulated ARHGDIB expression in alveolar epithelial cells. Silencing ARHGDIB significantly reduced oxidative stress inflammation, and promoted autophagy in LPS-treated MLE-12 cells. ARHGDIB knockdown modulated the PRKACB/NF-κB signaling pathway, thereby promoting autophagy and alleviating LPS-induced cellular injury.</p><p><strong>Conclusion: </strong>This regulatory mechanism significantly reduced oxidative stress and inflammatory responses in alveolar epithelial cells, highlighting the protective role of ARHGDIB silencing in LPS-induced lung injury.</p>","PeriodicalId":7536,"journal":{"name":"Allergologia et immunopathologia","volume":"53 5","pages":"36-44"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Knockdown of ARHGDIB promotes autophagy and reduces inflammation in LPS-induced alveolar epithelial cells via the PRKACB/NF-κB pathway.\",\"authors\":\"Haizhen Jin, Shuangxia Dong, Zhihui Li, Dai Xinjian\",\"doi\":\"10.15586/aei.v53i5.1362\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute lung injury (ALI) is a critical clinical condition with high mortality, necessitating the development of more effective therapeutic strategies. Rho Guanine nucleotide dissociation inhibitor (GDP) beta (ARHGDIB) has been shown to exert protective effects against noxious stimuli in various disease models.</p><p><strong>Objective: </strong>In this study, we investigated whether ARHGDIB knockdown had a protective effect on lipopolysaccharide (LPS)-induced injury in alveolar epithelial cells and elucidated its underlying molecular mechanisms.</p><p><strong>Material and methods: </strong>Mouse alveolar epithelial cells that were isolated from the lung of a 5-month-old female mouse (MLE-12) were treated with LPS, followed by ARHGDIB knockdown and overexpression of protein kinase A (PKA)-activated catalytic subunit β (PRKACB). Oxidative stress and apoptosis were assessed, while inflammatory cytokine levels were quantified using enzyme-linked immunosorbent serologic assays. Autophagy and PRKACB/nuclear factor <i>kappa B</i> (NF-κB) pathway activation was evaluated by Western blot analysis. Results: LPS upregulated ARHGDIB expression in alveolar epithelial cells. Silencing ARHGDIB significantly reduced oxidative stress inflammation, and promoted autophagy in LPS-treated MLE-12 cells. ARHGDIB knockdown modulated the PRKACB/NF-κB signaling pathway, thereby promoting autophagy and alleviating LPS-induced cellular injury.</p><p><strong>Conclusion: </strong>This regulatory mechanism significantly reduced oxidative stress and inflammatory responses in alveolar epithelial cells, highlighting the protective role of ARHGDIB silencing in LPS-induced lung injury.</p>\",\"PeriodicalId\":7536,\"journal\":{\"name\":\"Allergologia et immunopathologia\",\"volume\":\"53 5\",\"pages\":\"36-44\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-09-01\",\"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.v53i5.1362\",\"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}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergologia et immunopathologia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.15586/aei.v53i5.1362","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}
Knockdown of ARHGDIB promotes autophagy and reduces inflammation in LPS-induced alveolar epithelial cells via the PRKACB/NF-κB pathway.
Background: Acute lung injury (ALI) is a critical clinical condition with high mortality, necessitating the development of more effective therapeutic strategies. Rho Guanine nucleotide dissociation inhibitor (GDP) beta (ARHGDIB) has been shown to exert protective effects against noxious stimuli in various disease models.
Objective: In this study, we investigated whether ARHGDIB knockdown had a protective effect on lipopolysaccharide (LPS)-induced injury in alveolar epithelial cells and elucidated its underlying molecular mechanisms.
Material and methods: Mouse alveolar epithelial cells that were isolated from the lung of a 5-month-old female mouse (MLE-12) were treated with LPS, followed by ARHGDIB knockdown and overexpression of protein kinase A (PKA)-activated catalytic subunit β (PRKACB). Oxidative stress and apoptosis were assessed, while inflammatory cytokine levels were quantified using enzyme-linked immunosorbent serologic assays. Autophagy and PRKACB/nuclear factor kappa B (NF-κB) pathway activation was evaluated by Western blot analysis. Results: LPS upregulated ARHGDIB expression in alveolar epithelial cells. Silencing ARHGDIB significantly reduced oxidative stress inflammation, and promoted autophagy in LPS-treated MLE-12 cells. ARHGDIB knockdown modulated the PRKACB/NF-κB signaling pathway, thereby promoting autophagy and alleviating LPS-induced cellular injury.
Conclusion: This regulatory mechanism significantly reduced oxidative stress and inflammatory responses in alveolar epithelial cells, highlighting the protective role of ARHGDIB silencing in LPS-induced lung injury.
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.