Particulate matter₁₀-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression

Particulate matter₁₀ (PM₁₀) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM₁₀-treated murine mice models.

In female BALB/c mice, PM₁₀ was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered. Chitinase-1 inhibitor (CPX) 6 times over 3 weeks or dexamethasone 3 times in the last week were intraperitoneally administered. Two days after the last challenges, mice were euthanized. Messenger RNA sequencing using lung homogenates was conducted to evaluate signaling pathways.

PM₁₀ and/or OVA-induced airway inflammation and fibrosis murine models were established. CPX and dexamethasone ameliorated PM₁₀ or PM₁₀/OVA-induced airway hyper-responsiveness, airway inflammation, and fibrosis. CPX and dexamethasone also reduced levels of various inflammatory markers in lung homogenates. PM₁₀ and OVA also induced changes in mRNA expression across an extreme range of genes. CPX and dexamethasone decreased levels of mRNA expression especially associated with inflammation and immune regulation. They also significantly regulated asthma and asthma-related pathways, including the JACK-STAT signaling pathway.

Chitinase-1 suppression by CPX can regulate PM₁₀- and OVA-induced and aggravated airway inflammation and fibrosis via an asthma-related signaling pathway.