Human airway eosinophils exhibit preferential ...
Document type :
Article dans une revue scientifique: Article original
DOI :
PMID :
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Title :
Human airway eosinophils exhibit preferential reduction in STAT signaling capacity and increased CISH expression.
Author(s) :
Burnham, Mandy E [Auteur]
Koziol-White, Cynthia J [Auteur]
Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Bates, Mary E [Auteur]
Evans, Michael D [Auteur]
Bertics, Paul J [Auteur]
Denlinger, Loren C [Auteur]
Koziol-White, Cynthia J [Auteur]
Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Bates, Mary E [Auteur]
Evans, Michael D [Auteur]
Bertics, Paul J [Auteur]
Denlinger, Loren C [Auteur]
Journal title :
Journal of immunology (Baltimore, Md. : 1950)
Abbreviated title :
J Immunol
Volume number :
191
Pages :
2900-2906
Publisher :
The American Association of Immunologists
Publication date :
2013-09-15
Article status :
Publié
ISSN :
1550-6606
English keyword(s) :
Asthma
Bronchoalveolar Lavage Fluid
Eosinophils
Humans
Immunoblotting
Interleukin-5
Phosphorylation
Real-Time Polymerase Chain Reaction
STAT Transcription Factors
Signal Transduction
Suppressor of Cytokine Signaling Proteins
Bronchoalveolar Lavage Fluid
Eosinophils
Humans
Immunoblotting
Interleukin-5
Phosphorylation
Real-Time Polymerase Chain Reaction
STAT Transcription Factors
Signal Transduction
Suppressor of Cytokine Signaling Proteins
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Allergic asthma, a chronic respiratory disorder marked by inflammation and recurrent airflow obstruction, is associated with elevated levels of IL-5 family cytokines and elevated numbers of eosinophils (EOS). IL-5 family ...
Show more >Allergic asthma, a chronic respiratory disorder marked by inflammation and recurrent airflow obstruction, is associated with elevated levels of IL-5 family cytokines and elevated numbers of eosinophils (EOS). IL-5 family cytokines elongate peripheral blood EOS (EOS(PB)) viability, recruit EOS(PB) to the airways, and, at higher concentrations, induce degranulation and reactive oxygen species generation. Although airway EOS (EOS(A)) remain signal ready in that GM-CSF treatment induces degranulation, treatment of EOS(A) with IL-5 family cytokines no longer confers a survival advantage. Because the IL-5 family receptors have common signaling capacity, but are uncoupled from EOS(A) survival, whereas other IL-5 family induced endpoints remain functional, we tested the hypothesis that EOS(A) possess a JAK/STAT-specific regulatory mechanism (because JAK/STAT signaling is critical to EOS survival). We found that IL-5 family-induced STAT3 and STAT5 phosphorylation is attenuated in EOS(A) relative to blood EOS from airway allergen-challenged donors. However, IL-5 family-induced ERK1/2 phosphorylation is not altered between EOS(A) and EOS from airway allergen-challenged donors. These observations suggest EOS(A) possess a regulatory mechanism for suppressing STAT signaling distinct from ERK1/2 activation. Furthermore, we found, in EOS(PB), IL-5 family cytokines induce members of the suppressors of cytokine signaling (SOCS) genes, CISH and SOCS1. Additionally, following allergen challenge, EOS(A) express significantly more CISH and SOCS1 mRNA and CISH protein than EOS(PB) counterparts. In EOS(PB), long-term pretreatment with IL-5 family cytokines, to varying degrees, attenuates IL-5 family-induced STAT5 phosphorylation. These data support a model in which IL-5 family cytokines trigger a selective downregulation mechanism in EOS(A) for JAK/STAT pathways.Show less >
Show more >Allergic asthma, a chronic respiratory disorder marked by inflammation and recurrent airflow obstruction, is associated with elevated levels of IL-5 family cytokines and elevated numbers of eosinophils (EOS). IL-5 family cytokines elongate peripheral blood EOS (EOS(PB)) viability, recruit EOS(PB) to the airways, and, at higher concentrations, induce degranulation and reactive oxygen species generation. Although airway EOS (EOS(A)) remain signal ready in that GM-CSF treatment induces degranulation, treatment of EOS(A) with IL-5 family cytokines no longer confers a survival advantage. Because the IL-5 family receptors have common signaling capacity, but are uncoupled from EOS(A) survival, whereas other IL-5 family induced endpoints remain functional, we tested the hypothesis that EOS(A) possess a JAK/STAT-specific regulatory mechanism (because JAK/STAT signaling is critical to EOS survival). We found that IL-5 family-induced STAT3 and STAT5 phosphorylation is attenuated in EOS(A) relative to blood EOS from airway allergen-challenged donors. However, IL-5 family-induced ERK1/2 phosphorylation is not altered between EOS(A) and EOS from airway allergen-challenged donors. These observations suggest EOS(A) possess a regulatory mechanism for suppressing STAT signaling distinct from ERK1/2 activation. Furthermore, we found, in EOS(PB), IL-5 family cytokines induce members of the suppressors of cytokine signaling (SOCS) genes, CISH and SOCS1. Additionally, following allergen challenge, EOS(A) express significantly more CISH and SOCS1 mRNA and CISH protein than EOS(PB) counterparts. In EOS(PB), long-term pretreatment with IL-5 family cytokines, to varying degrees, attenuates IL-5 family-induced STAT5 phosphorylation. These data support a model in which IL-5 family cytokines trigger a selective downregulation mechanism in EOS(A) for JAK/STAT pathways.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Collections :
Submission date :
2023-11-10T15:28:14Z
2024-05-30T12:10:34Z
2024-05-30T12:10:34Z
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