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Effects of chitinase-1 inhibitor in obesity-induced and -aggravated asthma in a murine model

 Heejae Han  ;  Yong Jun Choi  ;  Hyerim Hong  ;  Chi Young Kim  ;  Min Kwang Byun  ;  Jae Hwa Cho  ;  Jae-Hyun Lee  ;  Jung-Won Park  ;  Taylor A Doherty  ;  Hye Jung Park 
 LIFE SCIENCES, Vol.334 : 122163, 2023-12 
Journal Title
Issue Date
Animals ; Asthma* / metabolism ; Bronchoalveolar Lavage Fluid ; Chitin ; Cytokines / metabolism ; Disease Models, Animal ; Fibrosis ; Lung / metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Obesity / complications ; Obesity / drug therapy ; Obesity / metabolism ; Ovalbumin / metabolism
Airway ; Asthma ; Chitinase ; Obesity
Aims: Despite recent investigations on the role of chitinase in asthma, its role in obesity-induced asthma has not been evaluated. Therefore, we investigated the roles of chitin, chitinase-1, and a chitinase-1 inhibitor (compound X, CPX) in a murine model.

Main methods: We assigned C57BL/6 mice to the ovalbumin (OVA) model or obesity model group. In the OVA model, mice received intraperitoneal OVA twice within a 2-week interval and intranasal OVA for 3 consecutive days. Additionally, chitin was intranasally administered for 3 consecutive days, and CPX was intraperitoneally injected three times over 5 days. In the obesity model, a high-fat diet (HFD) was maintained for 13 weeks, and CPX was intraperitoneally injected eight times over 4 weeks.

Key findings: In the OVA model, chitin aggravated OVA-induced airway hyper-responsiveness (AHR), increased bronchoalveolar lavage fluid (BALF) cell proliferation, increased fibrosis, and increased the levels of various inflammatory cytokines (including chitinase-1, TGF-β, TNF-α, IL-1 β, IL-6, IL-4, and IL-13). CPX treatment significantly ameliorated these effects. In the obesity model, HFD significantly increased AHR, BALF cell proliferation, fibrosis, and the levels of various inflammatory cytokines. Particularly, compared to the control group, the mRNA expression of chitinase, chitinase-like molecules, and other molecules associated with inflammation and the immune system was significantly upregulated in the HFD and HFD/OVA groups. Immunofluorescence analysis also showed increased chitinase-1 expression in these groups. CPX significantly ameliorated all these effects in this model.

Significance: This study showed that CPX can be an effective therapeutic agent in asthma, especially, obesity-induced and -aggravated asthma to protect against the progression to airway remodeling and fibrosis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chi Young(김치영)
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Park, Hye Jung(박혜정) ORCID logo https://orcid.org/0000-0002-1862-1003
Byun, Min Kwang(변민광) ORCID logo https://orcid.org/0000-0003-1525-1745
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
Cho, Jaehwa(조재화) ORCID logo https://orcid.org/0000-0002-3432-3997
Choi, Yong Jun(최용준) ORCID logo https://orcid.org/0000-0002-6114-2059
Hong, Hyerim(홍혜림)
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