| Project/Area Number |
10670549
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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 |
INOUE Hiromasa Kyushu University, Fac of Medicine, Assist Professor, 医学部, 助手 (30264039)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Koichiro Kyushu University, Fac of Med, Fellow, 医学部, 医員
古藤 洋 九州大学, 医学部, 助手 (10253452)
AIZAWA Hisamichi Clin Res Ctr, Fukuoka-higashi Ntl Hosp, Director, 臨床研究部, 臨床研究部長 (90175711)
KOMORI Masashi Kyushu University, Fac of Med, Fellow, 医学部, 医員
松本 幸一郎 九州大学, 医学部, 医員
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | bronchial asthma / airway inflammation / airway smooth muscle / eosinophil / eotaxin / interleukin-8 / 杯細胞 / 気道リモデリング / Ectaxin |
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| Research Abstract |
We examined the role of chemokines, interleukin-8 (IL-8) and eotaxin, in chronic airway inflammation and hyperresponsiveness. We also established an animal model of airway remodeling to study the mechanism of the development of airway remodeling.
Nitric oxide (NO) is increased in exhaled air of asthmatics, and we examined effects of NO synthase inhibitors on IL-8 levels in the airways and in airway inflammation and hyperresponsiveness in guinea pigs in vivo.. Pretreatment with NO synthase inhibitors had no effect on airway hyperresponsiveness or neutrophil accumulation immediately after ozone, but significantly inhibited the changes 5 h after ozone. NO synthase inhibitors also attenuated the increases of nitrite/nitrate levels in bronchoalveolar lavage fluid and the IL-8 mRNA expression in epithelial cells and in neutrophils in guinea pig airways 5 h after ozone. These results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsive
… More
ness after ozone exposure, presumably partly through the upregulation of IL-8.
We studied the effects of local administration of eotaxin on airway inflammation and hyperresponsiveness in guinea pigs in vivo. Significant eosinophilia in BALF was observed between 24 h and 7 d after eotaxin administration. In contrast, eotaxin did not affect airway response. We then studied the effects on airway responsiveness of subthreshold doses of interleukin-5, leukotriene D_4 (LTD_4), and platelet activating factor (PAF) combined with eotaxin. Neither interleukin-5 nor LTD4 affected airway response. After eotaxin treatment, PAF significantly enhanced airway responsiveness without further increases in eosinophil counts. These data indicate that eotaxin alone causes eosinophil accumulation in the airways but not hyperresponsiveness, and that an additional factor such as PAF is needed to activate eosinophils for the development of airway hyperresponsiveness.
Airway remodeling, such as goblet cell hyperplasia, thickening of the reticular layer beneath the epithelial basement membrane, and increased mass of airway smooth muscle, is important histological feature of chronic asthma. We established an animal model of airway remodeling, especially smooth muscle remodeling. Ovalbumin (OVA) was injected intraperitoneally to BALB/c mice. After sensitization, OVA were inhaled 3 times/weeks for 6 weeks. Lung tissues were histologically evaluated after hematoxylin-eosin and Massontrichrome stains 24 h after last challenge. Goblet cell hyperplasia and subepithelial eosinophil infiltration were observed after 3 antigen challenges. After 12 challenges, the amount of collagen beneath the basement membrane and the mass of smooth muscle were increased. These results suggest that repeated allergen inhalations induce airway remodeling including the increase of smooth muscle mass in mouse. Less
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