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

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-beta, TNF-alpha, IL-1 beta, IL-6, IL-4, and IL-13). CPX treatment significantly ameliorated these effects. In the obesity model, HFD significantly increased AHR, BALF cell pro-liferation, 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.

Automated summary

This study investigated the roles of chitin, chitinase-1, and a chitinase-1 inhibitor (compound X, CPX) in a murine model of asthma. The results showed that chitin aggravated airway inflammation and CPX treatment significantly ameliorated these effects. In obesity-induced asthma, CPX was also effective in reducing airway inflammation and fibrosis.