Chitinase 3‐like 1 protein plays a critical role in respiratory syncytial virus‐induced airway inflammation

Autor: Kyung Won Kim, Jae Myun Lee, Kuk‐Young Moon, Hye-Ran Cha, Jack A. Elias, Myung Hyun Sohn, Su Jin Hwang, Min Jung Kim, Doo Hee Shim, Chun Geun Lee, Jeon Han Park, Chang Mo Yang
Rok vydání: 2018
Předmět:
0301 basic medicine
Respiratory System
Immunology
Inflammation
Respiratory Syncytial Virus Infections
Asthma and Lower Airway Disease
CHI3L1
chitinase 3‐like 1 protein
Mice
03 medical and health sciences
0302 clinical medicine
Lower respiratory tract infection
medicine
Animals
Humans
Immunology and Allergy
Chitinase-3-Like Protein 1
Respiratory system
Child
Growth Substances
Lung
medicine.diagnostic_test
business.industry
type 2 immunity
respiratory system
medicine.disease
M2 Macrophage
Asthma
Respiratory Syncytial Viruses
Mice
Inbred C57BL
030104 developmental biology
Bronchoalveolar lavage
medicine.anatomical_structure
030228 respiratory system
Bronchiolitis
Case-Control Studies
lower respiratory tract infection
Cytokines
Original Article
bronchiolitis
Female
ORIGINAL ARTICLES
medicine.symptom
business
Zdroj: Allergy
ISSN: 1398-9995
0105-4538
Popis: 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.
Respiratory syncytial virus infection induces increased expression of BRP‐39 by macrophages and epithelial cells that is related to Th2 inflammation. A lack of BRP‐39 attenuates RSV‐induced airway inflammation and IL‐13 responses. BRP‐39 is an important regulator of RSV infection and suggested as a potential therapeutic target for RSV‐related respiratory illness.
Databáze: OpenAIRE
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