The ECRG4 cleavage product augurin binds the endotoxin receptor and influences the innate immune response during otitis media
Otitis media (OM), the most common disease of childhood, is typically characterized by bacterial infection of the middle ear (ME). Prominent features of OM include hyperplasia of the ME mucosa, which transforms from a monolayer of simple squamous epithelium with minimal stroma into a full-thickness...
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Published in | Frontiers in genetics Vol. 13; p. 932555 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
26.08.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Otitis media (OM), the most common disease of childhood, is typically characterized by bacterial infection of the middle ear (ME). Prominent features of OM include hyperplasia of the ME mucosa, which transforms from a monolayer of simple squamous epithelium with minimal stroma into a full-thickness respiratory epithelium in 2-3 days after infection. Analysis of the murine ME transcriptome during OM showed down-regulation of the tumor suppressor gene
that was temporally related to mucosal hyperplasia and identified stromal cells as the primary ECRG4 source. The reduction in
gene expression coincided with the cleavage of ECRG4 protein to release an extracellular fragment, augurin. The duration of mucosal hyperplasia during OM was greater in
mice, the number of infiltrating macrophages was enhanced, and ME infection cleared more rapidly. ECRG4-null macrophages showed increased bacterial phagocytosis. Co-immunoprecipitation identified an association of augurin with TLR4, CD14 and MD2, the components of the lipopolysaccharide (LPS) receptor. The results suggest that full-length ECRG4 is a sentinel molecule that potentially inhibits growth of the ME stroma. Processing of ECRG4 protein during inflammation, coupled with a decline in
gene expression, also influences the behavior of cells that do not express the gene, limiting the production of growth factors by epithelial and endothelial cells, as well as the activity of macrophages. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: W. Edward Swords, University of Alabama at Birmingham, United States Reviewed by: William C. Ray, Nationwide Children’s Hospital, United States Grzegorz Juszczak, Institute of Genetics and Animal Biotechnology (PAN), Poland This article was submitted to Genetics of Common and Rare Diseases, a section of the journal Frontiers in Genetics |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2022.932555 |