Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model

Abstract Otitis Media (OM) is characterized by epithelial abnormalities and defects in innate immunity in the middle ear (ME). Although, BPIFA1, a member of the BPI fold containing family of putative innate defence proteins is abundantly expressed by the ME epithelium and SNPs in Bpifa1 have been as...

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Main Authors:	Apoorva Mulay, Derek W. Hood, Debbie Williams, Catherine Russell, Steve D. M. Brown, Lynne Bingle, Michael Cheeseman, Colin D. Bingle
Format:	Article
Language:	English
Published:	Nature Publishing Group 2018-02-01
Series:	Scientific Reports
Online Access:	https://doi.org/10.1038/s41598-018-21166-7

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spelling	doaj-e65ef82b32dd466f8b1795d40269554f2020-12-08T06:00:35ZengNature Publishing GroupScientific Reports2045-23222018-02-018111210.1038/s41598-018-21166-7Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse modelApoorva Mulay0Derek W. Hood1Debbie Williams2Catherine Russell3Steve D. M. Brown4Lynne Bingle5Michael Cheeseman6Colin D. Bingle7Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of SheffieldMRC Mammalian Genetics Unit, MRC Harwell InstituteMRC Mammalian Genetics Unit, MRC Harwell InstituteAcademic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of SheffieldMRC Mammalian Genetics Unit, MRC Harwell InstituteOral and Maxillofacial Pathology, Department of Clinical Dentistry, University of SheffieldRoslin Institute, University of EdinburghAcademic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of SheffieldAbstract Otitis Media (OM) is characterized by epithelial abnormalities and defects in innate immunity in the middle ear (ME). Although, BPIFA1, a member of the BPI fold containing family of putative innate defence proteins is abundantly expressed by the ME epithelium and SNPs in Bpifa1 have been associated with OM susceptibility, its role in the ME is not well characterized. We investigated the role of BPIFA1 in protection of the ME and the development of OM using murine models. Loss of Bpifa1 did not lead to OM development. However, deletion of Bpifa1 in Evi1 Jbo/+ mice, a model of chronic OM, caused significant exacerbation of OM severity, thickening of the ME mucosa and increased collagen deposition, without a significant increase in pro-inflammatory gene expression. Our data suggests that BPIFA1 is involved in maintaining homeostasis within the ME under steady state conditions and its loss in the presence of inflammation, exacerbates epithelial remodelling leading to more severe OM.https://doi.org/10.1038/s41598-018-21166-7
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Apoorva Mulay Derek W. Hood Debbie Williams Catherine Russell Steve D. M. Brown Lynne Bingle Michael Cheeseman Colin D. Bingle
spellingShingle	Apoorva Mulay Derek W. Hood Debbie Williams Catherine Russell Steve D. M. Brown Lynne Bingle Michael Cheeseman Colin D. Bingle Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model Scientific Reports
author_facet	Apoorva Mulay Derek W. Hood Debbie Williams Catherine Russell Steve D. M. Brown Lynne Bingle Michael Cheeseman Colin D. Bingle
author_sort	Apoorva Mulay
title	Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model
title_short	Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model
title_full	Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model
title_fullStr	Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model
title_full_unstemmed	Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model
title_sort	loss of the homeostatic protein bpifa1, leads to exacerbation of otitis media severity in the junbo mouse model
publisher	Nature Publishing Group
series	Scientific Reports
issn	2045-2322
publishDate	2018-02-01
description	Abstract Otitis Media (OM) is characterized by epithelial abnormalities and defects in innate immunity in the middle ear (ME). Although, BPIFA1, a member of the BPI fold containing family of putative innate defence proteins is abundantly expressed by the ME epithelium and SNPs in Bpifa1 have been associated with OM susceptibility, its role in the ME is not well characterized. We investigated the role of BPIFA1 in protection of the ME and the development of OM using murine models. Loss of Bpifa1 did not lead to OM development. However, deletion of Bpifa1 in Evi1 Jbo/+ mice, a model of chronic OM, caused significant exacerbation of OM severity, thickening of the ME mucosa and increased collagen deposition, without a significant increase in pro-inflammatory gene expression. Our data suggests that BPIFA1 is involved in maintaining homeostasis within the ME under steady state conditions and its loss in the presence of inflammation, exacerbates epithelial remodelling leading to more severe OM.
url	https://doi.org/10.1038/s41598-018-21166-7
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Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model

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