Relationship between CC chemokine expression in the airways of severe asthmatics and steroid resistance

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: KEIO UNIVERSITY
• Principal Investigator: NAKAMURA Hidetoshi Keio University, School of Medicine, Assistant, 医学部, 助手 (00217879)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Takahiro Keio University, School of Medicine, Assistant, 医学部, 助手 (70306702) ; ASANO Koichiro Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (60192944) ; YAMAGUCHI Kazuhiro Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (30129712)
• Project Period (FY): 2002 – 2003
• Keywords: asthma / severity / eotaxin / steroid / bradykinin / TGF-β1 / oncostatin-M

Research Abstract

Among biomarkers of asthma severity studied, plasma eotaxin level was not significantly affected by corticosteroid treatment, and was associated with the severity of stable asthmatics even in the presence of steroid therapy. There was a significant correlation between the pretreatment levels of plasma eotaxin and the extent of functional improvement after steroid treatment in unstable asthmatics. These results suggest that plasma eotaxin level is a marker of disease activity and/or treatment response to steroids in unstable asthma.
Bradykinin concentrations in exhaled breath condensate in asthmatics were detectable but were not different from those in normal subjects. Eotaxin production in human fetal fibroblast (HFL-1) was slightly increased by Bradykinin. TNF-α strongly induced eotaxin production in this cell line which was moderately inhibited by the addition of oncostatin-M or TGF-β1. The inhibitory effects of steroid on eotaxin production were further enhanced by coincubation with TGF-β1.

Research Products

• [Publications] Tateno H, Nakamura H, et al.: "Plasma eotaxin level and severity of asthma treated with corticosteroid."Respir.Med.. (in press). (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 仲村秀俊, 石坂彰敏: "肺線維化におけるケモカインとケモカインレセプターの関与"分子呼吸器病. 6(4). 290-295 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Asano K, Shiomi T, et al.: "Leukotriene C_4 synthase gene A(-444)C polymorphism and clinical response to a cys-LT_1 antagonist, pranlukast, in Japanese patients with moderate asthma."Pharmacogenetics. 12. 565-570 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Minematsu N, Nakamura H, et al.: "Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema."Thorax. 58. 623-628 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tateno H, Nakamura H, Minematsu N, Nakajima T, Takahashi S, Nakamura M, Fukunaga K, Asano K, Lilly CM, Yamaguchi K.: "Plasma eotaxin level and severity of asthma treated with corticosteroid."Respir Med. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakamura H, Ishizaka A.: "Roles of chemokines and their receptors in the development of pulmonary fibrosis."Bunshi-Kokyukibyo (Respiratory Molecular Medicine). 6(4). 290-295 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Asano K, Shiomi T, Hasegawa N, Nakamura H, Kudo H, Matsuzaki T, Hakuno H, Fukunaga K, Shiomi T, Suzuki Y, Kanazawa M, Yamaguchi: "Leukotriene C_4 synthase gene A(-444)C polymorphism and clinical response to a cys-LT_1 antagonist, Pranlukast, in Japanese patients with moderate asthma."Pharmacogenetics. 12. 565-570 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Minematsu N, Nakamura H, Iwata M, Tateno H, Nakajima T, Takahashi S, Fujishima S, Yamaguchi K.: "Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema."Thorax. 58. 623-628 (2003)
  • Description: 「研究成果報告書概要(欧文)」より