Chitinase 3-like 1 protein plays a critical role in respiratory syncytial virus-induced airway inflammation.
Animals
Asthma
/ virology
Case-Control Studies
Child
Chitinase-3-Like Protein 1
/ adverse effects
Cytokines
/ metabolism
Female
Growth Substances
Humans
Inflammation
/ virology
Mice
Mice, Inbred C57BL
Respiratory Syncytial Virus Infections
/ complications
Respiratory Syncytial Viruses
Respiratory System
/ pathology
bronchiolitis
chitinase 3-like 1 protein
lower respiratory tract infection
respiratory syncytial viruses
type 2 immunity
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
06
12
2017
revised:
09
09
2018
accepted:
19
09
2018
pubmed:
8
11
2018
medline:
6
5
2020
entrez:
8
11
2018
Statut:
ppublish
Résumé
Chitinase 3-like 1 protein (CHI3L1) (YKL-40 in humans and breast regression protein [BRP]-39 in mice) is required for optimal allergen sensitization and Th2 inflammation in various chronic inflammatory diseases including asthma. However, the role of CHI3L1 in airway inflammation induced by respiratory viruses has not been investigated. The aim of this study was to investigate the relationship between CHI3L1 and airway inflammation caused by respiratory syncytial virus (RSV) infection. We measured YKL-40 levels in human nasopharyngeal aspirate (NPA) from hospitalized children presenting with acute respiratory symptoms. Wild-type (WT) and BRP-39 knockout (KO) C57BL/6 mice were inoculated with live RSV (A2 strain). Bronchoalveolar lavage fluid and lung tissue samples were obtained on day 7 after inoculation to assess lung inflammation, airway reactivity, and expression of cytokines and BRP-39. In human subjects, YKL-40 and IL-13 levels in NPA were higher in children with RSV infection than in control subjects. Expression of BRP-39 and Th2 cytokines, IL-13 in particular, was increased following RSV infection in mice. Airway inflammation caused by RSV infection was reduced in BRP-39 KO mice as compared to WT mice. Th2 cytokine levels were not increased in the lungs of RSV-infected BRP-39 KO mice. BRP-39 regulated M2 macrophage activation in RSV-infected mice. Additionally, treatment with anti-CHI3L1 antibody attenuated airway inflammation and Th2 cytokine production in RSV-infected WT mice. These findings suggest that CHI3L1 could contribute to airway inflammation induced by RSV infection. CHI3L1 could be a potential therapeutic candidate for attenuating Th2-associated immunopathology during RSV infection.
Sections du résumé
BACKGROUND
Chitinase 3-like 1 protein (CHI3L1) (YKL-40 in humans and breast regression protein [BRP]-39 in mice) is required for optimal allergen sensitization and Th2 inflammation in various chronic inflammatory diseases including asthma. However, the role of CHI3L1 in airway inflammation induced by respiratory viruses has not been investigated. The aim of this study was to investigate the relationship between CHI3L1 and airway inflammation caused by respiratory syncytial virus (RSV) infection.
METHODS
We measured YKL-40 levels in human nasopharyngeal aspirate (NPA) from hospitalized children presenting with acute respiratory symptoms. Wild-type (WT) and BRP-39 knockout (KO) C57BL/6 mice were inoculated with live RSV (A2 strain). Bronchoalveolar lavage fluid and lung tissue samples were obtained on day 7 after inoculation to assess lung inflammation, airway reactivity, and expression of cytokines and BRP-39.
RESULTS
In human subjects, YKL-40 and IL-13 levels in NPA were higher in children with RSV infection than in control subjects. Expression of BRP-39 and Th2 cytokines, IL-13 in particular, was increased following RSV infection in mice. Airway inflammation caused by RSV infection was reduced in BRP-39 KO mice as compared to WT mice. Th2 cytokine levels were not increased in the lungs of RSV-infected BRP-39 KO mice. BRP-39 regulated M2 macrophage activation in RSV-infected mice. Additionally, treatment with anti-CHI3L1 antibody attenuated airway inflammation and Th2 cytokine production in RSV-infected WT mice.
CONCLUSION
These findings suggest that CHI3L1 could contribute to airway inflammation induced by RSV infection. CHI3L1 could be a potential therapeutic candidate for attenuating Th2-associated immunopathology during RSV infection.
Identifiants
pubmed: 30402955
doi: 10.1111/all.13661
pmc: PMC7159489
doi:
Substances chimiques
CHI3L1 protein, human
0
Chil1 protein, mouse
0
Chitinase-3-Like Protein 1
0
Cytokines
0
Growth Substances
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
685-697Subventions
Organisme : Korea Health Industry Development Institute
ID : HI15C2971
Pays : International
Organisme : National Research Foundation of Korea
ID : NRF-2017R1A2B2004043
Pays : International
Organisme : NHLBI NIH HHS
ID : P01 HL114501
Pays : United States
Organisme : Korea Health Industry Development Institute
ID : HI13C0826
Pays : International
Organisme : Korea Health Industry Development Institute
ID : HI17C0104
Pays : International
Informations de copyright
© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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