• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2005 Fiscal Year Final Research Report Summary

Possible involvement of epithelial-smooth muscle functional relationship in developing airway hyperresponsiveness induced by Th2 cytokine.

Research Project

Project/Area Number 16590197
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

OIKE Masahiro  Kyushu University, Faculty of Medical Sciences, Associate Professor, 大学院・医学研究院, 助教授 (70271103)

Co-Investigator(Kenkyū-buntansha) ITO Yushi  Kyushu University, Faculty of Medical Sciences, Professor, 大学院・医学研究院, 教授 (80037506)
Project Period (FY) 2004 – 2005
Keywordsairway smooth muscle cells / muscle contractility / Th2 cytokines / matrix metalloprotease / myosin light chain kinase
Research Abstract

Predominance of Th2 cytokines compared to Th1 cytokines has been hypothesized to cause bronchial asthma. Major pathogenesis of bronchial asthma is inflammation and hyperresponsiveness of the airway. However, causal relationship between Th2 cytokines and the development of airway hyperresponsiveness has not been fully clarified. We have examined the effects of interleukin 4 (IL4) and 13 (IL13), Th2 cytokines, on the contractility of bovine tracheal smooth muscle cells (BTSMC). Pretreatment of BTSMC-embedded collagen gel lattice with IL4 suppressed ATP- and A23187-induced contraction of the gels, whereas IL13 markedly augmented the gel contraction. IL4 and IL13, however, did not affect the [Ca^<2+>]_i elevation and phosphorylation of contractile proteins induced by these stimuli in BTSMC, indicating that IL4 and IL13 do not affect the contractility of smooth muscle cells. We have observed that IL4 markedly and IL13 moderately increased the expression of matrix metalloprotease-1 (MMP-1) mRNA in BTSMC. Protein level of MMP-1 in the culture medium was also markedly increased by IL4, and moderately increased by IL13. The exogenous application of low concentration of MMP-1 induced the augmentation of the BTSMC-embedded collagen gels, and high concentration of MMP-1 leaded to the inhibition of gel contraction. Also, galardin, a non-specific inhibitor of MMP, suppressed both IL4- and IL13-induced effects on gel contraction. We have concluded from these results that Th2 cytokines induce the production of MMP-1 in airway smooth muscle cells, thereby digesting the extracellular matrix and changing tissue elasticity. We suppose these are partially responsible for the airway remodeling and hyperresponsiveness induced by Th2 cytokines. Furthermore, since airway epithelial cells are reported to generate MMP-1, we suppose that this mechanism plays a role in the possible functional interaction between epithelium and smooth muscle cells.

  • Research Products

    (7 results)

All 2006 2005 2004

All Journal Article (6 results) Book (1 results)

  • [Journal Article] Excess 1-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole.2005

    • Author(s)
      Cheng, W. et al.
    • Journal Title

      Toxicology and Applied Pharmacology 207・3

      Pages: 187-194

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of PRIP-1, a novel Ins(1,4,5)P_3 binding protein, in Ins(1,4,5)P_3-mediated Ca^<2+> signaling.2005

    • Author(s)
      Harada, K et al.
    • Journal Title

      Journal of Cellular Physiology 202・2

      Pages: 422-433

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Excess l-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole.2005

    • Author(s)
      Cheng, W., et al.
    • Journal Title

      Toxicology and Applied Pharmacology 207-3

      Pages: 187-194

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of PRIP-1, a novel Ins(1,4,5)P_3 binding protein, in Ins(1,4,5)P_3-mediated Ca^<2+> signaling.2005

    • Author(s)
      Harada, K., et al.
    • Journal Title

      Journal of Cellular Physiology 202-2

      Pages: 422-433

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sequential activation of RhoA and FAK/paxillin leads to ATP release and actin reorganization in human endothelium.2004

    • Author(s)
      Hirakawa, M et al.
    • Journal Title

      Journal of Physiology (London) 558・2

      Pages: 479-488

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sequential activation of RhoA and FAK/paxillin leads to ATP release and actin reorganization in human endothelium.2004

    • Author(s)
      Hirakawa, M., et al.
    • Journal Title

      Journal of Physiology (London) 558-2

      Pages: 479-488

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Annual Review 2006 呼吸器 (分担執筆)2006

    • Author(s)
      伊東祐之, 大池正宏, 小西秀平
    • Total Pages
      253
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2007-12-13  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi