オクニシ カツヒデ   Okunishi Katsuhide
  奥西 勝秀
   所属   東邦大学  医学部 医学科
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 A novel role of cysteinyl leukotrienes to promote dendritic cell activation in the antigen-induced immune responses in the lung.
掲載誌名 正式名:Journal of immunology (Baltimore, Md. : 1950)
ISSNコード:0022-1767
掲載区分国外
出版社 AMER ASSOC IMMUNOLOGISTS
巻・号・頁 173(10),pp.6393-402
著者・共著者 Katsuhide Okunishi,Makoto Dohi,Kazuyuki Nakagome,Ryoichi Tanaka,Kazuhiko Yamamoto
発行年月 2004/11/15
概要 Although the critical role of cysteinyl leukotrienes (cysLTs) in the inflammation, especially eosinophilic lung inflammation, in asthma has been well documented, their role in the early stage of Ag-specific immune response has not been completely clarified. In the present study, with a mouse model of asthma and in vitro studies we demonstrated that cysLTs potentiated dendritic cell (DC) functions such as Ag-presenting capacity and cytokine production. The cysLT-1 receptor antagonist (LTRA) strongly suppressed the activation of these DC functions and led to inhibition of subsequent not only Th2, but also Th1, responses in the early stage of immune response. Moreover, treatment with LTRA during the early stage of the immune response potently suppressed the development of Ag inhalation-induced eosinophilic airway inflammation, mucus production, and airway hyper-reactivity in vivo. Treatment with LTRA significantly increased PGE(2) production in the lung, and treatment with the cyclooxygenase inhibitor indomethacin abolished LTRA's suppressive effect on DCs and deteriorated the Th2 and Th1 responses and airway inflammation. With in vitro studies, we also confirmed that cysLTs production by DCs increased with LPS stimulation, and that LTRA directly suppressed the alloantigen-presenting capacity of DCs. These results suggested that cysLTs potentiate DC functions both in vivo and in vitro, and that LTRA could be beneficial to suppress the initial immune response in many immune-mediated disorders beyond asthma.
DOI 10.4049/jimmunol.173.10.6393
PMID 15528379