1998 Fiscal Year Final Research Report Summary
Pathogenesis and treatment of common cold-induced exacerbations of bronchial asthma
| Project/Area Number |
09670594
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAYA Mutsuo Department of Geriatric Medicine, Tohoku University School of Medicine, Research Associate, 医学部・附属病院, 助手 (60261640)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Bronchial asthma / Rhinovirus / Airway / Glucocorticoid / Erythromycin / ICAM-1 / Cytokines / LDL-receptor |
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| Research Abstract |
1. To examine the role of the low density lipoprotein (LDL) receptor on the infection of minor subgroup human rhinovirus, we cultured human tracheal epithelial cells. Human rhinovirus type 2 (RV2) was released into supernatants, and RV2 infection unregulated the production of interleukin (IL)-lbeta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha in supernatants. Antibodies to the LDLreceptor inhibited RV2 infection and decreased the production of cytokines after RV2 infection. Furthermore, RV2 infection unregulated LDLreceptor mRNA expression. These finding suggest that minor subgroup rhinovirus can infect human airway epithelial cells via a LDL receptor on the cells. 2. To examine whether rhinovirus infection impairs epithelial barrier functions, human rhinovirus type 14(RV14) was infected to cultures of human tracheal epithelial cells. Hydrogen peroxide (H_2O_<>) increased electrical conductance (G) across the epithelial cell sheet measured with Ussing's chamber methods. RV14 infection potentiated H_2O_<>-induced increases in G and [^3H]-mannitol flux through the cultured epithelium in IL-1beta pretreated conditions. IL-1beta enhanced intercellular adhesion molecule-l (ICAM-l) expression. These findings suggest that RV14 may reduce barrier functions in the airway epithelium in association with upregulation of ICAM-1beta. We examined the effects of dexamethasone, erythromycin and H'ATPase inhibitor bafilomycin on RVl4 release and cytokine content in the supernatants, and found that these treatment reduced virus Liter of supernatants and cytokines production of IL-1beta, IL-6, IL-8 and TNF-alpha in supernatants. These treatment may inhibit rhinovirus infection and modulate airway inflammation caused by rhinovirus infection.
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[Publications] M.terajima, M.Yamaya, K.Sekizawa, S.Okinaga, T.Suzuki, N.Yamada, K.Nakayama, T.Ohrui, T.Suzuki, N.Yamada, K.Nakayama, T.Ohrui, T.Oshima, Y.Numazaki, H.Sasaki.: "Rhinovirus infection of primary cultures of human tracheal epithelium : role of ICAM-1 and IL-1beta." Am.J.Physiol. 273. L794-L759 (1997)
Description
「研究成果報告書概要(欧文)」より
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