| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
To study the mechanisms of rhinovirus (RV) infection-induced bromchial asthma exacerbations, we examined mucin production in cultured human tracheal epithelial cells and submucosal gland cells, the number of Streptococcus pneumoniae (S.pneumoniae) adhering to the cultured human tracheal epithelial cells, the effects of RV infection on the eosinophil chemotaxis, and the effects of macrolide antibiotics on RV infection. We found that RV infection induced the production of various mucin mRNA including MUC5AC and increased MUC5AC content in supernatants in tracheal epithelial cells and submucosal gland cells. Culture supernatants of submucosal gland cells after RV infection increased the eosinophil chemotaxis. RV infection increased the number of S.pneumoniae adhering to the epithelial cells. Antibodies to regulate on activation, normal T cells expressed and secreted (RANTES) and granulocyte macrophage-colony stimulating factor (GM-CSF), inhibited the eosinophil chemotaxis, and reduced the
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content of RANTES and GM-CSF in culture supernatants increased after RV infection. RANTES and GM-CSF released from submucosal gland cells might induce eosinophil chemotaxis in RV infection. Because RV infection induced the production of a receptor for platelet activating factor (PAF-R), the receptor for S.pneumoniae, and a PAF-R inhibitor reduced the number of S.pneumoniae, adhesion of S.pneumoniae to the epithelial cells may be associated with the bacterial bronchopneumonia after RV infection. A macrolide antibiotic erythroycin reduced RV titers in supernatants and RV RNA replication in cultured tracheal epithelial cells. The reduced production of intercellular adhesion molecule-1 (ICAM-1), the receptor for major type RV and the reduced number of acidic endosomes might. be associated with the inhibitory effects of erythromycin on RV infection. Erythromycin may also modulate airway inflammation by reducing the production of pro-inflammatory cytokines and ICAM-1 induced by RV infection. Less
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