Alternaria alternata-induced airway hyperresponsiveness in BALB/c mice
To better evaluate the physiological response of mice to A. alternata and the potential for C391 to limit this response, we used the forced oscillation technique to measure respiratory resistance in response to methacholine (MCh) challenge in A. alternata -sensitized/challenged BALB/c mice (Addison, Morse, Robichaud, Daines & Ledford, 2017). A. alternata treatment resulted in an increase in airway hyperresponsiveness (AHR) to MCh as reported by total airway resistance (Max Rrs % over baseline) that intensified with each dose of MCh. In comparison, mice treated with HBSS alone responded to MCh challenges with stable and relatively low total airway resistance(Figure 7) . In contrast to A. alternata- treated mice, mice receiving both A. alternata and C391 exhibited significantly reduced total airway resistances that were not significantly different than total airway resistances observed in HBSS-treated control animals. These results suggest PAR2 inhibition by C391 is effective at protecting against the development of AHR in an acute, A. alternata -sensitized/challenged murine model.