| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
BACKGROUND : Mucus hypersecretion, caused by hypertrophy and hyperplasia of mucous cells in the airway, is one of the major pathologic properties, and gets potentially involved in a severe disease of asthma. Therefore, they have been assumed to be an ultimate key feature to elucidation of their pathogenesis and a promising therapeutic target in asthma. Previous studies have exhibited the overexpression of human chloride channel, hCLCA1, associated with mucus overproduction and hypersecretion in asthmatic epithelium. These results suggested that the chloride channel may be involved in hypersecretory disorder in asthma. To confirm that these molecules are implicated in allergic inflammation in the airway, we investigated epithelial expression of mCLCA3, murine homologue of hCLCA1, in a mouse model of allergic pulmonary inflammation. OBJECTIVE : The present study examines whether mCLCA3 relates to mucus overproduction and hypersecretion in immunized mice. METHODS : BALB/c male mice were i
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mmunized intraperitoneally with ovalbumin (OVA), and were subsequently exposed to aerosolized OVA solution once for all through the expose term (tentatively called acute asthmatic model), for 7 consecutive days (i.q. subacute asthmatics), or for 21 consecutive days (i.q. chronic asthmatics). The excised lung tissues were fixed in 4% paraformaldehyde and were thin-sliced to sections. The lung sections were stained with Giemsa, periodic acid-Schiff (PAS), and were hybridized to digoxigenin (DIG)-labeled RNA probe that is complimentary to the desired mCLCA3 mRNA. Post-hybridized tissues were immunostained with tyramide-enhanced technique. RESULTS : Eosinophilic infiltration and mucus cell hyper- and metaplasia were increased prominently in 7-day and 21-day Ag-exposed mice (p<0.05). MCLCA3 mRNA expression were enhanced considerably in subacute and chronic asthmatic mucosa in the airway (p<0.05). Furthermore, significant correlation between mCLCA3 expression and mucus score was observed. CONCLUSION : Mucus overproduction and mCLCA3 overexpression were demonstrated in the lung of the model of allergic inflammation (r=0.84, p<0.05). MCLCA3, homologue of hCLCA1, may participate in mucus overproduction in allergic pulmonary inflammation. Less
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