Role of airway epithelial cells in the accumulation and activation of T cells in allergic airway inflammation

气道上皮细胞在过敏性气道炎症中 T 细胞积累和激活中的作用

• 批准号: 10670533
• 负责人: TAKIZAWA Hajime
• 金额: $ 2.05万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670533/
• 关键词: Allergic airway inflammation; Bronchial asthma; Chemokine gene expression; Airway epithelial cell; T cell; Chemotactic factor; Adhesion molecule; co-stimulatory molecule; アレルギー性気道炎症; ケモカイン; RANTES; ICAM-1

Airway epithelial cells are known to play an integral role in the airway responses thorough the production of cytokines/chemokines important in the pathogenesis of bronchial asthma. We could demonstrated that : 1) human airway epithelial cells had potentials to express and release RANTES and TARC , both being chemotactic for T lymphocytes. 2) They expressed adhesion molecules and co-stimulatory molecules such as ICAM-1 (CD54). B7-1 CCD80) and B7-2 (CD86). When T lymphocytes were co-incubated with airway epithelial cells, they were stimulated to release IL-4 and IL-13, which are important Th2-type cytokines. Therefore, airway epithelial cells can regulate not only cell migration and attachment but also activation of T cells. 3) In murine models of allergic asthma, there was an intense expression of TARC in the airway epithelium by immunohistochemistry. Above observations strongly suggested that airway epithelial cells play an important role in the regulation of T lymphocyte functions in allergic airway inflammation found in asthma.

众所周知，呼吸道上皮细胞通过产生在哮喘发病机制中起重要作用的细胞因子/趋化因子，在呼吸道反应中发挥不可或缺的作用。结果表明：1)人呼吸道上皮细胞具有表达和释放RANTES和TARC的潜能，两者对T淋巴细胞均具有趋化作用。2)表达黏附分子和共刺激分子，如ICAM-1(CD54)。B7-1 CCD80)和B7-2(CD86)。当T淋巴细胞与呼吸道上皮细胞共同孵育时，它们被刺激释放重要的Th2型细胞因子IL-4和IL-13。因此，呼吸道上皮细胞不仅可以调节细胞的迁移和附着，还可以调节T细胞的激活。3)免疫组织化学显示，变态反应性哮喘小鼠呼吸道上皮细胞有TARC的强阳性表达。上述观察结果有力地提示，在哮喘的过敏性气道炎症中，呼吸道上皮细胞在T淋巴细胞功能的调节中起着重要作用。

项目成果

Takayuki Ohtoshi et al.: "Diesel exhaust particles(DEP)stimulate human airway epithelial cells to produce cytokines relevent to airway inflammation in vitro." J.Allergy Clin.Immunol.101. 778-785 (1998)

Takayuki Ohtoshi 等人：“柴油机尾气颗粒 (DEP) 刺激人体气道上皮细胞产生与体外气道炎症相关的细胞因子。”

Matsumoto K., Hashimoto S., Gon Y., Nakamura T., Takizawa H., Horie T.: "Nacethylcystein inhibits IL-1α-induced IL-8 secretion by bronchial epithelial cells"Respir. Med.. 92. 512-515 (1998)

Matsumoto K.、Hashimoto S.、Gon Y.、Nakamura T.、Takizawa H.、Horie T.：“乙酰半胱氨酸抑制支气管上皮细胞 IL-1α 诱导的 IL-8 分泌”Med.. 92。 512- 515 (1998)

S. Kawasaki, H. Takizawa, T. Ohtoshi, N. Takeuchi, T. Kohyama, H. Nakamura, T. Kasama, K. Kobayashi, K. Nakahara, Y. Morita, K. Yamamoto: "Roxithromycin Inhibits Cytokine Production and Neutrophile Attochment with Human Bronchial Epithelial cells in vitro

S. Kawasaki、H. Takizawa、T. Ohtoshi、N. Takeuchi、T. Kohyama、H. Nakamura、T. Kasama、K. Kobayashi、K. Nakahara、Y. Morita、K. Yamamoto：“罗红霉素抑制细胞因子的产生和

T.Ohtoshi, H. Takizawa, H. Okazaki, S. Kawasaki, N. Takeuchi, K. Ohta, K.Ito: "Diesel exhaust particles(DEP) stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro"J. Allergy Clin. Immunol.. 101. 778-785 (199

T.Ohtoshi、H. Takizawa、H. Okazaki、S. Kawasaki、N. Takeuchi、K. Ohta、K.Ito：“柴油机尾气颗粒 (DEP) 刺激人体气道上皮细胞产生与体外气道炎症相关的细胞因子”

M.Kobayashi, T.Niitsuma, T. Hayashi, M. Tanaka, H. Takizawa: "Interferon-γ inhibits the growth of human bronchial epithelial cells independently of transforming growth factor-B-1 and nitric oxide (No)"Biochem. Biophys. Res. Comman.. 224. 126-130 (1998)

M.Kobayashi、T.Niitsuma、T. Hayashi、M. Tanaka、H. Takizawa：“干扰素-γ 抑制独立转化生长因子-B-1 和一氧化氮的人支气管上皮细胞的生长（否）”Biochem。生物物理学研究。224。126-130（1998）