Adjuvant effect of inhaled particulate matter containing free radicals following house-dust mite induction of asthma in mice
Introduction: Exposures to particulate matter (PM) from combustion sources can exacerbate preexisting asthma. However, the cellular and molecular mechanisms by which PM promotes the exacerbation of asthma remain elusive. We used a house dust mite (HDM)-induced mouse model of asthma to test the hypothesis that inhaled DCB230, which are PM containing environmentally persistent free radicals (EPFRs), will aggravate asthmatic responses. Methods: Groups of 8–10-week-old C57BL/6 male mice were exposed to either air or DCB230 aerosols at a concentration of 1.5 mg/m3 4 h/day for 10 days with or without prior HDM-induction of asthma. Results: Aerosolized DCB230 particles formed small aggregates (30–150 nm). Mice exposed to DCB230 alone showed significantly reduced lung tidal volume, overexpression of the Muc5ac gene, and dysregulation of 4 inflammation related genes, Ccl11, Ccl24, Il-10, and Tpsb2. This suggests DCB230 particles interacted with the lung epithelium inducing mucous hypersecretion and restricting lung volume. In addition to reduced lung tidal volume, compared to respective controls, the HDM + DCB230-exposed group exhibited significantly increased lung tissue damping and up-regulated expression of Muc5ac, indicating that in this model, mucous hypersecretion may be central to pulmonary dysfunction. This group also showed augmented lung eosinophilic inflammation accompanied by an up-regulation of 36 asthma related genes. Twelve of these genes are part of IL-17 signaling, suggesting that this pathway is critical for DCB230 induced toxicity and adjuvant effects in lungs previously exposed to HDM. Conclusion: Our data indicate that inhaled DCB230 can act as an adjuvant, exacerbating asthma through IL-17-mediated responses in a HDM mouse model.
Noël, Alexandra; Harmon, Ashlyn C.; Subramanian, Balamurugan; Perveen, Zakia; Aryal, Ankit; Legendre, Kelsey; Zaman, Hasan; Paulsen, Daniel B.; Varner, Kurt J.; Dugas, Tammy R.; and Penn, Arthur L., "Adjuvant effect of inhaled particulate matter containing free radicals following house-dust mite induction of asthma in mice" (2023). School of Graduate Studies Faculty Publications. 213.