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2001 Fiscal Year Final Research Report Summary

Molecular mechanisms of chemokine gene expression in allergic airway inflammation : Selective induction of eotaxin and TARC by Th2 cytokines in airway epithelial cells

Research Project

Project/Area Number 12670551
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

TAKIZAWA Hajime  Dpt Respir Med, The University of Tokyo, Associat Professor, 医学部・附属病院, 助教授 (80171578)

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)
Project Period (FY) 2000 – 2001
Keywordseotaxin / Th2 cytokine / transcription factor / airway epithelial cell / bronchial asthma
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.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Abes, Takizawa H, Sugawara I, Kudohs.: "Diesel exhaust (DE) induced cytokine expression in human bronchial epithelial cells A study with anew cell exposure system to fleshly generate"Am. J. Respir. Cell. Mol. Biol.. 22. 2960-303 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Takizawa, S.Abe, T.Ohtoshi, S.Kawasaki, K.Takami, M.Desaki, I.Sugawara, S.Hashimoto, A.Azuma, K.Nakahara, S.Kudoh: "Diesel exhaust particles (DEP) upregulate expression of intercellular adhesion molecule (ICAM-1) in human bronchial epithelial cells"Clin. Exp. Immunol.. 120. 356-362 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Desaki, H.Takizawa, T.Kasama, K.Kobayasi, Y.Morita, K.Yamamoto: "Nuclear factor-kappa B activation in silica induced interleukin 8 production by human bronchial epithelial cells"Cytikine. 12. 1257-1260 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Kawasaki, H.Takazawa, K.Takami, M.Desaki, H.Okazaki, T.Kasama, K.Kobayashi, K.Yamamoto, K.Nakahara, M.Tanaka, M.Segai, T.Ohtoshi: "Benzene extracted components are important in the major activity of diesel exhaust particles (DEP) : Effect on IL-8 gene expression in human bronchial epithelial cells"Am. J. Respir Cell Mol Biol. 24. 419-426 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Kawasaki, H.Takizawa, H.Yoneyama, T.Nakayama, R.Fujisawa, M.Izumizaki, T.Imai, O.Yoshie, I.Honma, K.Matsushima: "Intervention of TARC Attenuates The Development of Allergic Airway Inflammation and Hyper responsiveness in Mice"J Immunol. 166. 2055-2062 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takami K, Takuwa N, Okazaki H, Kobayashi M, Ohtoshi T, Kawasaki S, Yamamoto K, Nakamura T, Tanaka M, Nakahara K, Takuwa Y, Takizawa H.: "Interferon-gamma inhibits hepatocyte growth factor stimulated cell proliferation of human bronchial epithelial cells up regulation dip27 (Kip1) cyclin dependent kinase inhibitor"Am. J. Respir. Cell. Moll. Biol.. 26. 231-238 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 滝澤 始: "気道上皮細胞 アレルギーナビゲーター"メディカルビュー社. 202-203 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Takizawa, S. Abe, T. Ohtoshi, S. Kawasaki, K. Takami, M. Desaki, I. Sugawara, S.Hashimoto, A. Azuma, K. Nakahara, S. Kudoh :: "Diesel exhaust particles ( DEP ) upregulate expression of intercellular adhesion molecule(ICAM)-1 in human bronchial epithelial cells"Clin.Exp.Immunol.. 120. 356-362 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M Desaki, H Takizawa, T Kasama, K Kobayashi, Y Morita, K Yamamoto.: "Nuclear factor-kappa B activation in silica-induced interleukin 8 production by human bronchial epithelial cells"Cytokine. 12. 1257-1260 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Kita, Y. Harihara, M. Hirata, K. Kusaka, K. Sano, M. Mori, M. Ito, H. Yoshino, A. Nakao, H.Takizawa, H. Hirai, K. Kubota, T. Takayama, H. Kawarasaki, K. Maekawa, M. Makuuchi :: "Adult-to-adult living-related liver transplantation for hepatitis B-related cirrhosis in Japan : two case reports"Transplant.Proc.. 32. 2189-2192 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hajime Takizawa, Mitsuru Tanaka, Kazutaka Takami, Takayuki Ohtoshi, Koji Ito, Masaru Satoh, Yasumasa Okada, Fumihiro Yamasawa, Akira Umeda, Kazuhiko Nakahara.: "Increased Expression of Transforming Growth Factor-β 1 in Small Airway Epithelium from Tobacco Smokers and Patients with Chronic Obstructive Pulmonary Disease (COPD)"Am J Respir Crit Care Med. 163. 1476-1483 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin Kawasaki, Hajime Takizawa, Kazutaka Takami, Masashi Desaki, Hitoshi Okazaki, Tsuyoshi Kasama, Kazuo Kobayashi, Kazuhiko Yamamoto, Kazuhiko Nakahara, Mitsuru Tanaka, Masaru Sagai, Takayuki Ohtoshi.: "Benzene-extracted components are important for the major activity of diesel exhaust particles ( DEP ) : Effect on IL-8 gene expression in human bronchial epithelial cells"Am J Respir Cell Mol Biol. 24. 419-426 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin Kawasaki, Hajime Takizawa, Hiroyuki Yoneyama, Takashi Nakayama, Ryuichi Fujisawa, Masahiko Izumizaki, Toshio Imai, Osamu Yoshie, Ikuo Homma, Kouji Matsushima.: "Intervention of TARC Attenuates The Development of Allergic Airway Inflammation and Hyperresponsiveness in Mice"J Immunol. 166. 2055-2062 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazutaka Takami, Noriko Takuwa, Hitoshi Okazaki, Takayuki Ohtoshi, Makoto Dohi, Kazuhiko Yamamoto, Toshikazu Nakamura, Mitsuru Tanaka, Kazuhiko Nakahara, Yoh Takuwa , Hajime Takizawa :: "Interferon γ Inhibits Hepatocyte Growth Factor-Stimulated Cell Proliferation of Human Bronchial Epithelial Cells : Upregulation of p27kip1 Cyclin-Dependent kinase Inhibitory"Am J Respir Cell Mol Biol. in press.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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