Inhibitory Effects of the Mucoactive Agent, Fudosteine, on Leukocyte Elastase-induced Lung Inflammation and Goblet Cell Metaplasia in the Mouse

Exposure of murine airways to leukocyte elastase (LE) induces inflammation and goblet cell metaplasia in the lung. Our aim in this study was to investigate the effects of the mucoactive agent, fudosteine, on these LE-induced effects in the murine lung. Balb/c mice were exposed to LE (10U/25μL/mouse) or to saline (25μL) intratracheally on days 1 and 8, and then treated with fudosteine (50μg/g body weight) or saline intraperitoneally from day 8 to day 12. On day 13, mice were sacrificed, and bronchoalveolar lavage fluid (BALF) and lung tissues were obtained. Lung tissues were examined by alcian blue/periodic acid-Schiff (PAS) staining to evaluate mucous glycoconjugates. BALF cells were counted and differentiated in culture, and the protein concentration in BALF samples were measured. Levels of interleukin (IL) -1β, IL-6, and keratinocyte-derived chemokine (KC) were measured in BALF samples by enzyme-linked immunosorbent assay (ELISA). Goblet cell metaplasia, as determined by PAS staining, was significantly higher in the bronchiolar epithelium of lung exposed to LE than in the saline-treated control. Total protein concentration, the number of neutrophils, lymphocytes and total cell number in BALF were all significantly increased by LE administration. These effects of LE were inhibited by treatment with fudosteine. In addition, the LE-induced increases in IL-1β, IL-6, and KC were significantly inhibited by the treatment with fudosteine. These results indicate that fudosteine regulates LE-associated lung diseases via modulation of inflammation and goblet cell metaplasia.