Innate epithelial and functional differences in airway epithelium of children with acute wheeze
BackgroundEarly childhood wheeze is a major risk factor for asthma. However, not all children who wheeze will develop the disease. The airway epithelium has been shown to be involved in asthma pathogenesis. Despite this, the airway epithelium of children with acute wheeze remains poorly characterize...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1606915/full |
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| author | Kevin Looi Kevin Looi Kevin Looi Thomas Iosifidis Thomas Iosifidis Thomas Iosifidis Thomas Iosifidis Saraya Harrison Saraya Harrison Stephen M. Stick Peter LeSouef Peter LeSouef Peter LeSouef Ingrid A. Laing Ingrid A. Laing Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic |
| author_facet | Kevin Looi Kevin Looi Kevin Looi Thomas Iosifidis Thomas Iosifidis Thomas Iosifidis Thomas Iosifidis Saraya Harrison Saraya Harrison Stephen M. Stick Peter LeSouef Peter LeSouef Peter LeSouef Ingrid A. Laing Ingrid A. Laing Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic |
| author_sort | Kevin Looi |
| collection | DOAJ |
| description | BackgroundEarly childhood wheeze is a major risk factor for asthma. However, not all children who wheeze will develop the disease. The airway epithelium has been shown to be involved in asthma pathogenesis. Despite this, the airway epithelium of children with acute wheeze remains poorly characterized.MethodsUpper airway epithelial cells (AEC) from children with acute wheeze and non-wheeze controls were cultured and expanded. Markers of epithelial lineage (Cytokeratin (KRT)-5, −19) and vimentin were assessed via qPCR and immunocytochemistry. Inflammatory cytokines (Interleukin (IL)-1β, −6, and −8) were measured using ELISA. Tight junction (TJ) protein expression and barrier integrity were determined via In-Cell Western and paracellular permeability assays, respectively.ResultsUpper AECs from children with acute wheeze had significantly higher KRT19 and lower vimentin gene expression compared to non-wheeze controls but similar KRT5 levels. Similar staining intensities of KRT5 and KRT19 proteins were observed in both cohorts. IL-6 and IL-8 levels were not significantly different, but IL-1β was increased in cultures from children with acute wheeze compared to controls. Tight junction protein expression of claudin-1, occludin and ZO-1 were significantly lower in acute wheeze cohorts, concomitant with increased paracellular permeability.ConclusionAirway epithelium of children experiencing acute wheeze appears abnormal, primarily with compromised epithelial barrier integrity. |
| format | Article |
| id | doaj-art-b8aeb52b21ea4a718407d86ca02412a6 |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-b8aeb52b21ea4a718407d86ca02412a62025-08-20T03:08:36ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-07-011310.3389/fcell.2025.16069151606915Innate epithelial and functional differences in airway epithelium of children with acute wheezeKevin Looi0Kevin Looi1Kevin Looi2Thomas Iosifidis3Thomas Iosifidis4Thomas Iosifidis5Thomas Iosifidis6Saraya Harrison7Saraya Harrison8Stephen M. Stick9Peter LeSouef10Peter LeSouef11Peter LeSouef12Ingrid A. Laing13Ingrid A. Laing14Anthony Kicic15Anthony Kicic16Anthony Kicic17Anthony Kicic18Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, AustraliaSchool of Population Health, Curtin University, Bentley, WA, AustraliaCentre for Child Health Research, The University of Western Australia, Nedlands, WA, AustraliaWal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, AustraliaSchool of Population Health, Curtin University, Bentley, WA, AustraliaCentre for Child Health Research, The University of Western Australia, Nedlands, WA, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins of Institute of Medical Research, Nedlands, WA, AustraliaCentre for Child Health Research, The University of Western Australia, Nedlands, WA, AustraliaSchool of Medical, Molecular and Forensic Sciences, Murdoch University, Perth, WA, AustraliaDepartment of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands, WA, AustraliaWal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, AustraliaCentre for Child Health Research, The University of Western Australia, Nedlands, WA, AustraliaDepartment of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands, WA, AustraliaWal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, AustraliaCentre for Child Health Research, The University of Western Australia, Nedlands, WA, AustraliaWal-yan Respiratory Research Centre, The Kids Research Institute Australia, The University of Western Australia, Nedlands, WA, AustraliaSchool of Population Health, Curtin University, Bentley, WA, AustraliaCentre for Child Health Research, The University of Western Australia, Nedlands, WA, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins of Institute of Medical Research, Nedlands, WA, AustraliaBackgroundEarly childhood wheeze is a major risk factor for asthma. However, not all children who wheeze will develop the disease. The airway epithelium has been shown to be involved in asthma pathogenesis. Despite this, the airway epithelium of children with acute wheeze remains poorly characterized.MethodsUpper airway epithelial cells (AEC) from children with acute wheeze and non-wheeze controls were cultured and expanded. Markers of epithelial lineage (Cytokeratin (KRT)-5, −19) and vimentin were assessed via qPCR and immunocytochemistry. Inflammatory cytokines (Interleukin (IL)-1β, −6, and −8) were measured using ELISA. Tight junction (TJ) protein expression and barrier integrity were determined via In-Cell Western and paracellular permeability assays, respectively.ResultsUpper AECs from children with acute wheeze had significantly higher KRT19 and lower vimentin gene expression compared to non-wheeze controls but similar KRT5 levels. Similar staining intensities of KRT5 and KRT19 proteins were observed in both cohorts. IL-6 and IL-8 levels were not significantly different, but IL-1β was increased in cultures from children with acute wheeze compared to controls. Tight junction protein expression of claudin-1, occludin and ZO-1 were significantly lower in acute wheeze cohorts, concomitant with increased paracellular permeability.ConclusionAirway epithelium of children experiencing acute wheeze appears abnormal, primarily with compromised epithelial barrier integrity.https://www.frontiersin.org/articles/10.3389/fcell.2025.1606915/fullacute wheezeairway epitheliumbarrier integritycell cultureconditional reprogramming |
| spellingShingle | Kevin Looi Kevin Looi Kevin Looi Thomas Iosifidis Thomas Iosifidis Thomas Iosifidis Thomas Iosifidis Saraya Harrison Saraya Harrison Stephen M. Stick Peter LeSouef Peter LeSouef Peter LeSouef Ingrid A. Laing Ingrid A. Laing Anthony Kicic Anthony Kicic Anthony Kicic Anthony Kicic Innate epithelial and functional differences in airway epithelium of children with acute wheeze Frontiers in Cell and Developmental Biology acute wheeze airway epithelium barrier integrity cell culture conditional reprogramming |
| title | Innate epithelial and functional differences in airway epithelium of children with acute wheeze |
| title_full | Innate epithelial and functional differences in airway epithelium of children with acute wheeze |
| title_fullStr | Innate epithelial and functional differences in airway epithelium of children with acute wheeze |
| title_full_unstemmed | Innate epithelial and functional differences in airway epithelium of children with acute wheeze |
| title_short | Innate epithelial and functional differences in airway epithelium of children with acute wheeze |
| title_sort | innate epithelial and functional differences in airway epithelium of children with acute wheeze |
| topic | acute wheeze airway epithelium barrier integrity cell culture conditional reprogramming |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1606915/full |
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