Endoplasmic reticulum-unfolded protein response signalling is altered in severe eosinophilic and neutrophilic asthma.

Animals Asthma / metabolism Endoplasmic Reticulum / metabolism Humans Inflammation / metabolism Mice Neutrophils / metabolism Signal Transduction Unfolded Protein Response
allergic lung disease asthma asthma mechanisms

Journal

Thorax
ISSN: 1468-3296
Titre abrégé: Thorax
Pays: England
ID NLM: 0417353

Informations de publication

Date de publication:
05 2022
Historique:
received: 11 08 2020
accepted: 06 07 2021
pubmed: 13 9 2021
medline: 15 4 2022
entrez: 12 9 2021
Statut: ppublish

Résumé

The significance of endoplasmic reticulum (ER) stress in asthma is unclear. Here, we demonstrate that ER stress and the unfolded protein response (UPR) are related to disease severity and inflammatory phenotype. Induced sputum (n=47), bronchial lavage (n=23) and endobronchial biopsies (n=40) were collected from participants with asthma with varying disease severity, inflammatory phenotypes and from healthy controls. Markers for ER stress and UPR were assessed. These markers were also assessed in established eosinophilic and neutrophilic murine models of asthma. Our results demonstrate increased ER stress and UPR pathways in asthma and these are related to clinical severity and inflammatory phenotypes. Genes associated with ER protein chaperone ( Heightened ER stress is associated with severe eosinophilic and neutrophilic inflammation in asthma and may play a crucial role in the pathogenesis of asthma.

Identifiants

DOI: 10.1136/thoraxjnl-2020-215979 PMID: 34510013
pubmed: 34510013
pii: thoraxjnl-2020-215979
doi: 10.1136/thoraxjnl-2020-215979
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

443-451

Informations de copyright

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Prabuddha S Pathinayake (PS)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
ORCID: 0000-0002-4947-5918

David W Waters (DW)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.

Kristy S Nichol (KS)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.

Alexandra C Brown (AC)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.

Andrew T Reid (AT)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.
ORCID: 0000-0001-5751-7025

Alan Chen-Yu Hsu (AC)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.

Jay C Horvat (JC)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.

Lisa G Wood (LG)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.

Katherine J Baines (KJ)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.

Jodie L Simpson (JL)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
ORCID: 0000-0002-3626-680X

Peter G Gibson (PG)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
NHMRC Centre for Clinical Research Excellence in Severe Asthma, New Lambton Heights, New South Wales, Australia.

Philip M Hansbro (PM)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.
Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia.

Peter A B Wark (PAB)

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia peter.wark@newcastle.edu.au.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
NHMRC Centre for Clinical Research Excellence in Severe Asthma, New Lambton Heights, New South Wales, Australia.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Réticulum endoplasmique › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Granulocytes neutrophiles › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Endoplasmic reticulum-unfolded protein...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Réponse aux protéines mal repliées › Endoplasmic reticulum-unfolded protein...