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

Abstract

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.

• Authors: Min Jung Kim, Doo Hee Shim, Hye-Ran Cha, Kuk-Young Moon, Chang Mo Yang, Su Jin Hwang, Kyung Won Kim, Jeon Han Park, Chun Geun Lee, Jack A Elias, Myung Hyun Sohn, Jae Myun Lee
• Journal: Allergy (Allergy) Vol. 74 Issue 4 Pg. 685-697 (04 2019) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 30402955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Chemical References

• CHI3L1 protein, human
• Chil1 protein, mouse
• Chitinase-3-Like Protein 1
• Cytokines
• Growth Substances

Topics

• Animals
• Asthma (virology)
• Case-Control Studies
• Child
• Chitinase-3-Like Protein 1 (adverse effects, analysis)
• Cytokines (metabolism)
• Female
• Growth Substances
• Humans
• Inflammation (virology)
• Mice
• Mice, Inbred C57BL
• Respiratory Syncytial Virus Infections (complications)
• Respiratory Syncytial Viruses
• Respiratory System (pathology, virology)