| Project/Area Number |
12670551
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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 | The University of Tokyo |
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Principal Investigator |
TAKIZAWA Hajime Dpt Respir Med, The University of Tokyo, Associat Professor, 医学部・附属病院, 助教授 (80171578)
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| Co-Investigator(Kenkyū-buntansha) |
DESAKI Masashi Dpt Respir Med, The University of Tokyo, Assistant Professor, 医学部・附属病院, 助手 (30251250)
OKAZAKI Hitoshi Dpt Respir Med, The University of Tokyo, Assistant Professor, 医学部・附属病院, 助手 (80261973)
TAKAMI Kazutaka Dpt Respir Med, The University of Tokyo, Assistant Professor, 医学部・附属病院, 助手
KAWASAKI Shin Dpt Respir Med, The University of Tokyo, Assistant Professor, 医学部・附属病院, 助手 (80334407)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | eotaxin / Th2 cytokine / transcription factor / airway epithelial cell / bronchial asthma / サイトカイン / 遺伝子調節 / アレルギー性炎症 / 治療薬剤 |
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| Research Abstract |
Airway epithelium-drived chemokines are believed to play important roles in the pathogenesis of allergic airway inflammatory diseases such as bronchial asthma. However, it remains unclear how certain chemokines are predominant in such airway inflammation ; for example, eosinophils in asthma and neutrophils in chrnic bronchitis, respectively. We studied the effect of Th-2 type cytokines such as IL-4 and IL-13 in the selective upregulation in chemokine gene expression in airway epithelial cells. We found that IL-4 and IL-13 both stimulated eotaxin gene expression, which is considered to be crucial in eosinophil recruitment in the airways. In contrast, these Th2 cytokines downregulated IL-8 gene expression, which is well known to be a potent neutrophil chemoattaractant. Further, IL-13 clearly induced STAT6 activation, an important step for the eotaxin transcription, but downregulated NFκB transcativation. Airway epithelial cells harvested from asthmatic subjects after informed consent, tended to show more eotaxin production than those from normal and bronchitis patients. These observations demonstrated that Th2 cytokines may play an important role in the selective induction of certain chemokines in allergic airway inflmmation.
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