Loss of versican and production of hyaluronan in lung epithelial cells are associated with airway inflammation during RSV infection.

Autor:	Kellar GG; Department of Defense, United States Army, Washington, USA; Benaroya Research Institute, Seattle, Washington, USA; Department of Immunology, University of Washington, Seattle, Washington, USA., Barrow KA; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA., Rich LM; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA., Debley JS; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA., Wight TN; Benaroya Research Institute, Seattle, Washington, USA., Ziegler SF; Benaroya Research Institute, Seattle, Washington, USA; Department of Immunology, University of Washington, Seattle, Washington, USA., Reeves SR; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA; Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA. Electronic address: stephen.reeves@seattlechildrens.org.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100076. Date of Electronic Publication: 2020 Nov 21.
DOI:	10.1074/jbc.RA120.016196
Abstrakt:	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. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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