Experimental Lung Research最新文献

{"title":"Hypobaric hypoxia promotes the production of IL-10 of lung NKT cells in HAPE rats to fight inflammation.","authors":"Dewei Li, Chun Wang, Zhaoquan Su, Jiaxue Ma, Weina Kong, Lingling Dong, Xuemei Wei, Xiumin Ma","doi":"10.1080/01902148.2025.2515361","DOIUrl":"https://doi.org/10.1080/01902148.2025.2515361","url":null,"abstract":"<p><p><b>Background:</b> There are environment-dependent pro-inflammatory and anti-inflammatory pathways during exposure to high altitudes. Although inhibiting the inflammatory pathway can alleviate high altitude pulmonary edema (HAPE), it is currently unclear whether inflammation is the cause of edema or the result of edema in HAPE-afflicted patients. Natural killer T (NKT) cells are a subset of T cells that play an important role in a variety of lung diseases. However, its specific role in HAPE remains unclear. <b>Methods:</b> HAPE rat model was established under hypobaric hypoxia condition. To investigate the role of NKT cells in HAPE, phenotypic and functional changes of NKT cells and their subpopulations were analyzed by flow cytometry. To further investigate the effect of TNF-α on NKT cells, rats were given intraperitoneal injection of TNF-α, and then, NKT cells were characterized by flow cytometry. Subsequently, the levels of TNF-α in the lungs and spleens of rats were detected by ELISA, and HAPE rats were treated with curcumin. <b>Results:</b> Compared with normal control, the ratio of TNF-α and IL-10 secreted by lung NKT cells was decreased in HAPE rats induced by hypoxia. Further analysis showed that the mean fluorescence intensity (MFI) of TNF-α in NKT cells did not change significantly, but the MFI of IL-10 increased significantly. Moreover, the MFI of IL-10 produced by TNF-α-treated rat lung NKT cells was higher, which was completely different from spleen NKT cells. ELISA experiments indicated that TNF-α was enriched in the lung tissue of rats regardless of hypoxia, and the level of TNF-α in lung tissue was upregulated after hypoxia. Furthermore, when HAPE rats were treated with curcumin, the MFI of IL-10 in the NKT cell subsets decreased. <b>Conclusions:</b> NKT cells produce high levels of IL-10, which inhibits the production of lung inflammation in HAPE rats. With the increase of TNF-α level, the inhibitory effect of lung NKT cells on inflammation was further enhanced. When the level of TNF-α decreases, the anti-inflammatory effect of NKT cells also weakens accordingly. Hence, NKT cells play a protective role in HAPE rat lungs.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"38-49"},"PeriodicalIF":1.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish as a model for investigating <i>Klebsiella pneumoniae</i>-driven lung injury and therapeutic targets.","authors":"Jian Ye, Lei Lu, Xiao-Hong Rui, Mei-di Ren, Fan Tu, Zhong-Bo Shang, Jun Liu","doi":"10.1080/01902148.2025.2472328","DOIUrl":"10.1080/01902148.2025.2472328","url":null,"abstract":"<p><p><b>Background:</b> Lung injury induced by Klebsiella pneumoniae infection presents a significant challenge, with complex molecular mechanisms driving tissue damage and immune dysregulation. This study aimed to establish a zebrafish model of K. pneumoniae-induced lung injury to explore the underlying molecular mechanisms involved in tissue damage, immune responses, and development.</p><p><p><b>Methods:</b> A zebrafish model was developed by injecting K. pneumoniae into the swim bladder at 96 h post-fertilization (hpf). The immune response, including neutrophil migration and cytokine secretion, was assessed through histological analysis and quantitative measures. Transcriptomic analysis was performed to evaluate gene expression changes related to lung development, immune regulation, and metabolism. The role of the TGF-β signaling pathway in immune response and tissue repair was investigated using the TGF-β inhibitor SB 431542.</p><p><p><b>Results:</b> Infection with K. pneumoniae induced rapid neutrophil migration and the secretion of inflammatory cytokines such as IL-6, IL-1β, TNF-α, and TNF-β, similar to immune responses seen in mouse models. Transcriptomic analysis revealed significant alterations in genes involved in lung development, immune responses, and metabolic pathways, underscoring the broad impact of infection on physiological regulation. The TGF-β signaling pathway was found to play a dual role: it promoted immune cell recruitment and cytokine secretion but suppressed developmental genes, delaying tissue repair. Treatment with SB 431542 reduced neutrophil aggregation, lowered cytokine levels, and restored gene expression related to development and repair.</p><p><p><b>Conclusions:</b> This zebrafish model effectively mimics K. pneumoniae-induced lung injury, offering valuable insights into the molecular mechanisms of tissue damage and immune dysregulation. Targeting the TGF-β signaling pathway holds therapeutic potential for reducing inflammation and promoting tissue repair, providing a foundation for the development of new treatment strategies for lung infections.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"11-22"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP4-mediated deubiquitination of SRC-1 regulates macrophage polarization and asthma inflammation.","authors":"Lina Yan, Yun Shen, Jing Song, Liang Liu, Zhuang Ma","doi":"10.1080/01902148.2025.2506373","DOIUrl":"10.1080/01902148.2025.2506373","url":null,"abstract":"<p><p><b>Background:</b> Asthma, the most common chronic respiratory disorder affecting individuals of all ages, is driven by inflammation that leads to airway hyperresponsiveness, airway wall remodeling, and mucus production. While inhaled corticosteroids remain the primary treatment despite their limitations, further research into the molecular mechanisms of asthma is needed to identify new therapeutic targets. <b>Methods:</b> A mouse model of asthma was created by treating mice with OVA. HE and PAS staining were used to detect histopathology. Gene and protein expression levels were assessed using qPCR, Western blot, and ELISA. The relationship between USP4 and SRC-1 was examined using Co-IP assay. The ubiquitination levels of SRC-1 were detected using IP assay while macrophage polarization was analyzed by flow cytometry. <b>Results:</b> The ovalbumin-induced mouse model of asthma exhibited a large quantity of inflammatory cell infiltration, proliferation of goblet cells, and increased mucus secretion. SRC-1 expression was upregulated in an OVA-induced mouse model of asthma. Downregulation of SRC-1 reduced macrophage polarization to the M1 phenotype, protecting against OVA-induced asthma, whereas SRC-1 overexpression inhibited M2 macrophage polarization by suppressing the NF-kB signaling pathway. Furthermore, USP4 was found to deubiquitinate SRC-1, enhancing its protein stability. The regulatory axis between USP4 and SRC-1 was validated <i>in vivo.</i> <b>Conclusion:</b> This study demonstrates that USP4 regulates the deubiquitination of SRC-1, which inhibits M2 macrophage polarization and reduces asthma-related inflammation. These findings suggest that USP4 and SRC-1 may serve as potential therapeutic targets for asthma treatment.HighlightsSRC-1 is upregulated in OVA-induced asthma and correlated to macrophage.SRC-1 knockdown reduces M1 macrophage polarization and airway inflammation in the asthma model.SRC-1 overexpression or USP4 overexpression suppresses IL-4-induced M2 polarization via the NF-κB pathway.USP4 regulates the deubiquitination of SRC-1, influencing macrophage polarization and inflammation.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"50-63"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Store-operated Ca²⁺ entry contributes to the ASM phenotype transition in asthma.","authors":"Hangqi Ni, Ting Li, Junjun Chen, Yuying Wei, Mengling Xia, Qing Wang","doi":"10.1080/01902148.2025.2486951","DOIUrl":"https://doi.org/10.1080/01902148.2025.2486951","url":null,"abstract":"<p><strong>Aim of the study: </strong>Phenotype modulation of airway smooth muscle cells (ASMC), characterized by a shift toward a more proliferative and synthetic phenotype from contractile cells, plays a crucial role in airway remodeling in asthma. STIM1 and Orai1, key components of store-operated Ca²⁺ entry (SOCE), have been demonstrated to enhance ASMC proliferation and migration. This study investigated the impact of STIM1/Orai1-mediated SOCE on ASMC phenotype transition and extracellular matrix (ECM) deposition in asthma.</p><p><strong>Materials and methods: </strong>The ASMCs were treated with PDGF-BB and SOCE inhibitors. Immunocytochemistry staining, enzyme-linked immunosorbent assay, and western blot assay were employed to detect the ASMC's proliferation as well as the expressions of contractile proteins, inflammatory cytokines and ECM. Moreover, the effect of SOCE repression in ECM deposition were evaluated in an asthmatic mouse model.</p><p><strong>Results: </strong>ASMCs from airways of mice were treated with PDGF-BB to induce the 'proliferative/synthetic' phenotype. We observed elevated expressions of STIM1 and Orai1 in phenotype-switched ASMCs, along with enhanced SOCE. SKF-96365 and RO2959, which target of STIM1/Orai1, could significantly inhibit SOCE activation in ASMCs. Moreover, these SOCE inhibitors mitigated the elevated proliferation rate, decreased the secretion of inflammatory cytokines and restored the reduced levels of contractile proteins in phenotype-switched ASMCs induced by PDGF-BB. Furthermore, we observed that PDGF-BB-induced 'proliferative/synthetic' ASMCs exhibited increased production of ECM components, including collagen I and fibronectin, as well as metalloproteinases (MMPs) such as MMP2 and MMP9, all of which were effectively inhibited by SKF-96365 and RO2959. <i>In vivo</i> experiments also demonstrated that SOCE inhibitors decreased ECM deposition and MMPs production in the asthmatic mouse model.</p><p><strong>Conclusions: </strong>These findings underscored the significant role of STIM1/Orai1-mediated SOCE in ASMC phenotype modulation and its impact on the excessive ECM deposition driven by ASMCs. Thus, our findings suggest that STIM1/Orai1-mediated SOCE may contribute to airway remodeling in asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"23-37"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of PRDX6 in the protective role of MANF in acute lung injury in rats.","authors":"Xiuli Yang, Xueying Xiao, Leiying Zhou, Yujun Shen, Lixia Wang, Qiying Shen","doi":"10.1080/01902148.2025.2454032","DOIUrl":"10.1080/01902148.2025.2454032","url":null,"abstract":"<p><p><b>Aim/Purpose of the study:</b> Acute lung injury (ALI) is a severe respiratory disease with high mortality, mainly due to overactivated oxidative stress and subsequent pyroptosis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an inducible secretory endoplasmic reticulum (ER) stress protein, inhibits lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the exact molecular mechanism remains unclear. Peroxiredoxin 6 (PRDX6), a peroxidase with a dual enzymatic function, is essential in regulating oxidative stress, which is closely associated with ALI. Furthermore, PRDX6 is an interacting protein of MANF. Therefore, this study aims to investigate the role of PRDX6 in the protective effect of MANF on ALI.</p><p><p><b>Materials and Methods:</b> In this study, we used LPS to establish the LPS-induced ALI model. Recombinant human MANF was administrated to wide-type (WT) and PRDX6 knockout (PRDX6^-/-) rats.</p><p><p><b>Results:</b> In WT rats, MANF reversed the increases of PRDX6, ROS overgeneration, and pyroptosis-related protein-Gasdermin D (GSDMD) induced by LPS challenge. In PRDX6^-/- rats, ROS generation, the protein level of GSDMD-N, and lung injury were not significantly decreased after human recombinant MANF administration in LPS-induced ALI.</p><p><p><b>Conclusions:</b> PRDX6 is involved in the protective role of MANF on ALI. It is a key target molecule for MANF to exert ALI inhibitory effects.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"1-10"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from hypoxic alveolar epithelial cells promote the phenotypic transformation of pulmonary artery smooth muscle cells via the Rap1 pathway","authors":"Guifang Sun, Fangyun Zhao, Yusen Feng, Fei Liu, Xingrui Liu, Yue Jiang, Yating Gao, Jian Hu, Feifei Zhou, Yongju Yang, Zhiqin Du, Caiyan Zhu, Bin Liu","doi":"10.1080/01902148.2024.2398994","DOIUrl":"https://doi.org/10.1080/01902148.2024.2398994","url":null,"abstract":"Background: Hypoxic pulmonary hypertension (HPH) is one of the important pathophysiological changes in chronic pulmonary heart disease. Hypoxia promotes the phenotypic transformation of pulmonary a...","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"13 1","pages":"160-171"},"PeriodicalIF":1.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model","authors":"David G. Hancock, Luke Berry, Naomi M. Scott, Kyle T. Mincham, William Ditcham, Alexander N. Larcombe, Barry Clements","doi":"10.1080/01902148.2024.2346320","DOIUrl":"https://doi.org/10.1080/01902148.2024.2346320","url":null,"abstract":"Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model.In a safety and tolerability ...","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"49 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice","authors":"Jialin Li, Kexuan Liu, Wenjuan He, Wencai Zhang, Yongchao Li","doi":"10.1080/01902148.2024.2339269","DOIUrl":"https://doi.org/10.1080/01902148.2024.2339269","url":null,"abstract":"Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the...","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"120 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential changes in expression of inflammatory mRNA and protein after oleic acid-induced acute lung injury","authors":"Regina Golding, Rudolf K. Braun, Lorenzo Miller, Michael Lasarev, Timothy A. Hacker, Allison C. Rodgers, Ava Staehler, Marlowe W. Eldridge, Awni Al-Subu","doi":"10.1080/01902148.2024.2341099","DOIUrl":"https://doi.org/10.1080/01902148.2024.2341099","url":null,"abstract":"Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pi...","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"44 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLCA1 exacerbates lung inflammation via p38 MAPK pathway in acute respiratory distress syndrome","authors":"Xing Lv, Long Zheng, Tianxiang Zhang, Weijia Wang, Yuanyuan Chen, Jing Li, Zhigui Cai, Xingxing Guo, Liqiang Song","doi":"10.1080/01902148.2024.2334262","DOIUrl":"https://doi.org/10.1080/01902148.2024.2334262","url":null,"abstract":"Recent research has revealed that airway epithelial calcium-activated chloride channel-1 (CLCA1) is implicated in the inflammation of multiple human respiratory diseases, but the specific role in a...","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"17 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}