4 research outputs found
Repeated exposure of house dust mite induces progressive airway inflammation in mice: Differential roles of CCL17 and ILâ13
Abstract We conducted a systematic evaluation of lung inflammation indued by repeated intranasal exposure (for 10 consecutive days) to a human aeroallergen, house dust mite (HDM) in BALB/c mice. Peak influx of neutrophils, monocytes/lymphocytes, and eosinophils was observed in bronchoalveolar lavage (BAL) on days 1, 7 and 11, respectively, and normalized to baseline by day 21. Peak elevations of Th2, myeloidâderived cytokines/chemokines and serum IgE were seen both in BAL and lung tissue homogenates between days 7 and 11, and declined thereafter; however, ILâ33 levels remained elevated from day 7 to day 21. Airway hyperreactivity to inhaled methacholine was significantly increased by day 11 and decreased to baseline by day 21. The lung tissue showed perivascular and peribronchial cuffing, epithelial hypertrophy and hyperplasia and goblet cell formation in airways by day 11, and resolution by day 21. Levels of soluble collagen and tissue inhibitors of metalloproteinases (TIMP) also increased reflecting tissue remodeling in the lung. Microarray analysis demonstrated a significant timeâdependent upâregulation of several genes including ILâ33, CLCA3, CCL17, CD4, CD10, CD27, ILâ13, Foxa3, ILâ4, ILâ10, and CD19, in BAL cells as well as the lung. Preâtreatment of HDM challenged mice with CCL17 and ILâ13 antibodies reduced BAL cellularity, airway hyperâresponsiveness (AHR), and histopathological changes. Notably, antiâILâ13, but not antiâCCL17 monoclonal antibodies (mAbs) reduced BAL neutrophilia while both mAbs attenuated eosinophilia. These results suggest that CCL17 has an overlapping, yet distinct profile versus ILâ13 in the HDM model of pulmonary inflammation and potential for CCL17âbased therapeutics in treating Th2 inflammation