| Co-Investigator(Kenkyū-buntansha) |
SAGARA Hironori Dokkyo University, School of Medicine, Assistant Professor, 医学部, 講師 (80275742)
FUKUSHIMA Yasutsugu Dokkyo University, School of Medicine, Assistant Professor, 医学部, 講師 (00254996)
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| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
One of the cardinal features of airway remodeling in asthrnais mucus gland hyperplasia and mucus overproduction and hypersecretion. Recently, a calcium-activated chloride channel, HCLCA1, was described that is upregulated by IL-9 and thought to regulate the expression of macros, such as MUCSA/C, a critical component of mucus in the airways.
We examined the expression of HCLCA1 in bronchial biopsy specimens of asthmatic subjects compared with those of control subjects and to demonstrate its relationship with IL-9, IL-9 receptor (IL-9R), and markers of mucus production. Bronchial biopsy specimens from subjects with asthmatic (n = 9), chronic bronchitis (n =10), sarcoidosis (n = 8) and healthy control (n =10) were stained with periodic acid-Schiff (PAS) to identify mucus glycoconjugates. IL-9-and IL-9R-positive cells were identified with in immunocytochemistly, and HCLCAI expression was detected by means of in situ hybridization with cRNA probes. We demonstrate significant increases in IL-
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9 (P <.001) and IL-9R (P <.05) immunoreactivity, as well as increased expression of HCLCAL mRNA (P <.001), in the epithelium of asthmatic patients compared with that found in control subjects. There was also an increase in the number of mucus-producing cells in biopsy specimens from asthmatic subjects (P<.001). HCLCA1 mRNA was strongly and selectively colocalized with PAS and IL-9R-positive epithelial cells. In particular, a strong positive correlation was observed between HCLCAI mRNA expression and IL-9-positive (r = 0.69, P <0.01) or 1L9R-positive (r = 0.79, P <.01) cells. An upregulation of HCLCA1 in the IL-9-responsive mucus-producing epithelium of asthmatic subjects compared with that seen in control subjects supports the hypothesis that this channel may be responsible, in part, for the overproduction of mucus in asthmatic subjects. These preliminary findings suggest the inhibition of HCLCAI may be an important new therapeutic approach to control mucus overproduction in chronic airway disorders. Less
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