2007 Fiscal Year Final Research Report Summary
Identification of transcription factors of contractile element of bronchial smooth muscle and its change in activity at airway hyperresponsiveness
| Project/Area Number |
18590246
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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 |
General pharmacology
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| Research Institution | Hoshi University |
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Principal Investigator |
MISAWA Miwa Hoshi University, Sch. of Pharm., Dept. of Pharmacol, Professor (20061294)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Yoshihiko Hoshi University, Sch. of Pharm., Dept. of Pharmacol, Assistant professor (00287848)
SAKAI Hiroyasu Hoshi University, Sch. of Pharm., Dept. of Pharmacol, Research Associate (00328923)
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| Project Period (FY) |
2006 – 2007
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| Keywords | bronchial asthma / airway hyperesponsiveness / Ca^<2+> sensitization / RhoA / transcription factor / statins / geranylgeranylation |
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| Research Abstract |
The mechanisms of pathogenesis of airway hyperresponsiveness(AHR) in allergic bronchial asthma were investigated pharmacologically and molecular biologically. The following results were obtained.
1. The contractile responsiveness to endothelin-1(ET-1) was increased in the bronchi isolated from rats subjected with repeated antigen challenges. In the augmented ET-1-induced contractility an increase in Ca^<2+> sensitization phenomenon was involved ; phosphorylations(activations) of CTI-17 and myosin light chain kinase were enhanced. 2. The expressions and activations of matrix metalloproteinase(MMP)-12 mRNA and protein of bronchial muscle were increased by repeated antigen challenges, suggesting that MMP-12 is responsible for ABR. 3. The probable transcription factors in bronchial smooth muscle which are activated by antigen exposure were examined covering it using nuclear extraction of the muscle by the method of protein/DNA array method. Among the transcription factors activated by exposuring antigen, it was found that USF-1, Sp1, NF-El, STAT5 and STAT6 are the transcription factors that have potency to bind to the elements of RhoA promoter area 4. Interleukin-13 was demonstrated to induce AHR through the transcription factor STAT6. 5. Lovastatin, one of the statins, when administered in vivo, inhibited the AHR in rats generated by repeated antigen challenges ex they It was shown that at that time, lovastatin also inhibited the translocation of RhoA to cell membrane. These findings suggest that statins may be effective for improvement of AHR in patients with bronchial asthma. 6. It was also suggested that glucocorticoids exert effectiveness for bronchial asthma by inhibiting the RhoA upregulation seen in the bronchial smooth muscle at antigen-exposure.
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Research Products
(65 results)
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[Journal Article] RhoA-kinase inhibitors augment the inhibitory effect of propofol on rat bronchial smooth muscle contaction2008
Author(s)
Hanazaki, M., Yokoyama, M., Morita, K., Kohjitani, A., Sakai, H., Chiba, Y. and Misawa, M.
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Journal Title
Anesthesia & Analgesia 106
Pages: 1765-1771
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] RhoA-kinase inhibitors augment the inhibitoryeffect of propofol on rat bronchial smooth muscle contaction.2008
Author(s)
Hanazaki, M., Yokoyama, M., Morita, K., Kohjitani, A., Sakai, H., Chiba, Y., Misawa, M.
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Journal Title
Anesthesia & Analgesia 106
Pages: 1765-1771
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Pharmacological studies on the respiratory tract (Rept.304):Effects of cigarette smoke exposure on airway responsiveness in C57BL/6Jmice2008
Author(s)
Matsuuchi, N., Ushikubo, H., Fujita, A., Sakai, H., Chiba, Y., Kamei, J.& Misawa, M.
Organizer
第81回日本薬理学会年会
Place of Presentation
横浜
Year and Date
20080300
Description
「研究成果報告書概要(和文)」より
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[Presentation] Pharmacological studies on the respiratory tract (Rept.305):Development of cigarette smoke-induced bronchial muscle hyperresponsiveness in rats depends on tar and nicotine contents2008
Author(s)
Fujita, A., Ushikubo, H., Chiba, Y., Sakai, H., Kamei, J. & Misawa, M.
Organizer
第81回日本薬理学会年会
Place of Presentation
横浜
Year and Date
20080300
Description
「研究成果報告書概要(和文)」より
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[Presentation] Pharmacological studies on the respiratory tract (Rept.308):Augmented sodium nitroprusside-induced venodilatation of nasal mucosa in vivo in rats with allergic rhinitis2008
Author(s)
Uto, F., Enzaka, J., Oshita, M., Sakai, H., Chiba, Y.& Misawa, M.
Organizer
第81回日本薬理学会年会
Place of Presentation
横浜
Year and Date
20080300
Description
「研究成果報告書概要(和文)」より
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[Presentation] Pharmacological studies on the respiratory tract (Rept.310):Increased expression of a disintegrin and metalloproteinase 8 in mice with allergic bronchial asthma2008
Author(s)
Onoda, S., Chiba, Y., Sakai, H., Hattori, Y., Maitani, Y., Kimura, S. & Misawa, M.
Organizer
第81回日本薬理学会年会
Place of Presentation
横浜
Year and Date
20080300
Description
「研究成果報告書概要(和文)」より
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[Presentation] Effects of cigarette smoke exposure on airway responsiveness in C57BL/6J mice.2008
Author(s)
Matsuuchi, N., Ushikubo, H., Fujita, A., Sakai, H., Chiba, Y., Kamei, J., Misawa, M.
Organizer
In The 81st Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Yokohama, Japan
Year and Date
2008-03-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Development of cigarette smoke-induced bronchial muscle hyperresponsiveness in rats depends on tar and nicotine contents.2008
Author(s)
Fujita, A., Ushikubo, H., Chiba, Y., Sakai, H., Kamei, J., Misawa, M.
Organizer
In The 81st Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Yokohama, Japan
Year and Date
2008-03-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Augmented sodium nitroprusside-venodilatation of nasal mucosa in vivo in rats with allergic rhinitis.2008
Author(s)
Uto, F., Enzaka, J., Oshita, M., Sakai, H., Chiba, Y., Misawa, M.
Organizer
In The 81st Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Yokohama, Japan
Year and Date
2008-03-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Increased expression of a sisintegrin and metalloproteinase 8 in mice with allergic vronchial asthma.2008
Author(s)
Onoda, S., Chiba, Y., Sakai, H., Hattori, Y., Maitani, Y., Kimura, S., Misawa, M.
Organizer
In The 81st Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Yokohama, Japan
Year and Date
2008-03-17
Description
「研究成果報告書概要(欧文)」より
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[Book] メディカルバイオ2008
Author(s)
千葉 義彦、三澤 美和
Total Pages
44-47
Publisher
株式会社オーム社
Description
「研究成果報告書概要(和文)」より
