Loss of versican and production of hyaluronan in lung epithelial cells are associated with airway inflammation during RSV infection
| Autor: | Kaitlyn A Barrow, Thomas N. Wight, Jason S Debley, L.M. Rich, Steven F. Ziegler, Stephen R. Reeves, Gerald G. Kellar |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
HA hyaluronan versican (VCAN) PMN polymorphonuclear neutrophils GAG glycosaminoglycan Biochemistry fibroblast Mice Versicans CCL chemokine (C-C motif) ligand FGM Fibroblast Growth Media BALF bronchoalveolar lavage fluid HAS hyaluronan synthase myeloid cell Hyaluronic Acid MO monocyte Lung HLF human lung fibroblast medicine.diagnostic_test biology HYAL hyaluronidase ALI air-liquid interface U937 Cells ELISA enzyme-linked immunosorbent assay respiratory system EO eosinophil ECM extracellular matrix MMP matrix metalloproteinase Hyaluronan synthase SPC-Cre surfactant protein-C Cre medicine.anatomical_structure HMW-HA high molecular weight HA Versican BEC bronchial epithelial cell medicine.symptom Bronchoalveolar Lavage Fluid Research Article TSG-6 TNFα-stimulated gene-6 viral immunology extracellular matrix Hyaluronoglucosaminidase Inflammation Respiratory Syncytial Virus Infections hyaluronan 03 medical and health sciences poly I:C polyinosinic:polycytidylic acid RSV espiratory syncytial virus medicine Animals Humans Fibroblast Molecular Biology ACK ammonium-chloride-potassium TSG-6 030102 biochemistry & molecular biology Monocyte epithelial cell TLR-3 toll-like receptor 3 Epithelial Cells cell adhesion Cell Biology Eosinophil LMW-HA lower molecular weight HA Coculture Techniques carbohydrates (lipids) 030104 developmental biology Bronchoalveolar lavage Immunology biology.protein Hyaluronan Synthases |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | Airway inflammation is a critical feature of lower respiratory tract infections caused by viruses such as respiratory syncytial virus (RSV). A growing body of literature has demonstrated the importance of extracellular matrix changes such as the accumulation of hyaluronan (HA) and versican in the subepithelial space in promoting airway inflammation; however, whether these factors contribute to airway inflammation during RSV infection remains unknown. To test the hypothesis that RSV infection promotes inflammation via altered HA and versican production, we studied an ex vivo human bronchial epithelial cell (BEC)/human lung fibroblast (HLF) coculture model. RSV infection of BEC/HLF cocultures led to decreased hyaluronidase expression by HLFs, increased accumulation of HA, and enhanced adhesion of U937 cells as would be expected with increased HA. HLF production of versican was not altered following RSV infection; however, BEC production of versican was significantly downregulated following RSV infection. In vivo studies with epithelial-specific versican-deficient mice [SPC-Cre(+) Vcan-/-] demonstrated that RSV infection led to increased HA accumulation compared with control mice, which also coincided with decreased hyaluronidase expression in the lung. SPC-Cre(+) Vcan-/- mice demonstrated enhanced recruitment of monocytes and neutrophils in bronchoalveolar lavage fluid and increased neutrophils in the lung compared with SPC-Cre(-) RSV-infected littermates. Taken together, these data demonstrate that altered extracellular matrix accumulation of HA occurs following RSV infection and may contribute to airway inflammation. In addition, loss of epithelial expression of versican promotes airway inflammation during RSV infection further demonstrating that versican's role in inflammatory regulation is complex and dependent on the microenvironment. |
| Databáze: | OpenAIRE |
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