2005 Fiscal Year Final Research Report Summary
Investigation of regulatory role and therapeutic potential of B7-DC in bronchial asthma
| Project/Area Number |
16590750
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
MATSUMOTO Koichiro Kyushu University, Hospital, Research Associate, 大学病院, 助手 (60325462)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Hiromasa Kyushu University, Hospital, Assistant Professor, 大学病院, 講師 (30264039)
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| Project Period (FY) |
2004 – 2005
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| Keywords | bronchial asthma / costimulatory molecule / B7-DC / IFN-γ / IL-13 / double-stranded RNA / P13 kinase / JNK |
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| Research Abstract |
It has been suggested that an immune regulation via costimulatory pathways might be involved in the pathogenesis of bronchial asthma. We have focused on B7-DC, and investigated its regulatory role in asthma using murine asthma models and cultured human airway epithelial cells.
(Elucidation of regulatory mechanisms by B7-DC on murine asthma models)
We showed that a treatment of allergen-sensitized mice with anti-B7-DC antibody augmented asthmatic responses after allergen challenge. This augmentation was not seen in IFN-γ-deficient mice or anti-IFN-γ antibody-treated mice, suggesting that B7-DC regulate asthmatic responses by an IFN-γ-dependent pathway. We next showed that allergen challenge induced the expression of B7-DC on dendritic cells in the lung and the expression was prevented by a treatment of mice with an IL-13-inhibitor. Although previous studies reported that the immuno-regulation by B7-DC partly involve indirect mechanisms via induction of other costimulatory molecules, eg.4-
… More
1 BBL or CD80/86, on dendritic cells, there was no significant induction of such molecules on the dendritic cells obtained from allergen-challenged lungs. These studies suggest that B7-DC, which is induced by IL-13, may regulate asthmatic responses via a mechanism independent of 4-1 BBL or CD80/86.
(Elucidation of inductive mechanisms of B7-DC on cultured human airway epithelial cells)
We showed that IL-13 and double-stranded RNA, a virus-associated molecule, induced the expression of B7-DC on cultured human airway epithelial cells. This induction was relatively resistant to the treatment with glucocorticoid. We next examined which pathways of protein kinase might be involved in the double-stranded RNA-induced expression of B7-DC. The expression of B7-DC was suppressed profoundly by P13 kinase inhibitors, and partly by a JNK inhibitor, but not by a p38MAP kinase inhibitor or an ERK inhibitor. The effects of kinase inhibitors on the expression of B7-DC were partly different from that on the production of IL-8 and RANTES from airway epithelial cells stimulated with double-stranded RNA. These studies suggest that the expression of B7-DC on airway epithelium may be mediated by an array of kinase pathways partly different from that involved in the chemokine production. Less
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Research Products
(2 results)
