RATIONALE: Caveolin-1 has emerged as a critical regulator of signaling pathways involved in lung fibrosis and inflammation. There are several reports of loss of caveolin-1 in fibrotic foci of lungs in patients with scleroderma lung disease and idiopathic lung fibrosis. Recently, loss of caveolin 1 in the lungs was reported following allergen challenge in a sensitized murine model of asthma. Therefore, the objective of this study was to investigate if caveolin-1 is deficient in patients with asthma compared to controls. METHODS: Monocytes were isolated from peripheral blood of asthmatics (all severities) and controls (n510). Endobronchial biopsy sections were obtained from 5 subjects with mild asthma and 4 healthy controls. Western blotting analysis and immunostaining was employed to study protein expression. Clinical markers of airway inflammation were collected. Caveolin-1 expression was also studied in a murine model of asthma. RESULTS: Caveolin-1 expression is reduced in peripheral blood monocytes, and in the lungs of asthmatics compared to controls. Loss of caveolin-1 is most evident in the bronchial epithelial cells of asthmatics. Low caveolin-1 is associated with increased collagen and tenascin deposition, and increased number of fibrocytes in the lungs of asthmatics vs. controls. Furthermore, caveolin-1 expression decreased following aspergillus challenge in a sensitized murine model of asthma. CONCLUSIONS: To our knowledge, this is the first investigation of a role for caveolin-1 in humans with asthma. We have demonstrated a novel regulatory protein that may play an important role in airway inflammation and fibrosis characteristic of asthma.
Full conference title:
American Academy of Allergy Asthma & Immunology
- AAAAI 2012 (68th)