| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
To investigate mechanisms of airway remodeling and to examine whether the airway remodeling can be reversible change by the treatment with glucocorticoids, we developed a murine asthma model with persistent airway inflammation, airway hyperresponsiveness (AHR), airway mucosal fibrosis, and examined effects of glucocorticoids on these changes. An aerosolization of ovalbumin (OVA, 0.5 mg/ml) to OVA-sensitized balb/c mice for 30 min once a day resulted in persistent airway inflammation and AHR to methacholine (Mch) throughout this experiment period. The inflammatory cell population in bronchoalveolar lavage (BAL) fluid consisted mainly of eosinophils on days 7 and 14 and of macrophages and lymphocytes on days 21 and 28. Low-level but persistent Th2 cytokine (IL-4 and IL-5) production in BAL fluid was observed during repeated OVA aerosolization. A relatively high concentration of IFN-γ was detected in the BAL fluid throughout the experimental periods. TGF-β was detected in BAL fluid on day 3 and persistent at remarkably high levels from day 7 through day 28. Elastica-Masson staining revealed submucosal thickening in trachea from day 7 through day 28. Dexamethasone treatment from day 7 to day 13 under repeated OVA aerosolization completely inhibited airway inflammation, AHR to Mch, and submucosal thickening in trachea by reducing inflammatory cell infiltration and edematous change. In addition, the dexamethasone treatment from day 21 to day 28 completely decreased TGF-β production in BAL fluid as well as submucosal thickening by reducing collagen deposition in trachea. These data suggest that persistence of airway inflammation and these cytokine (IL-4, IL-5, IFN-γ, and TGF-β) productions in airways may be involved in the development of airway remodeling (including collagen deposition in airways), and this mucosal collagen deposition in airways can be reversible change by the treatment with glucocorticoids.
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