Kurokawa Masatsugu, Konno Satoshi, Matsukura Satoshi, Kawaguchi Mio, Ieki Koushi, Suzuki Shintarou, Odaka Miho, Watanabe Shin, Homma Tetsuya, Sato Masayuki, Takeuchi Hiroko, Hirose Takashi, Huang Shau-Ku, Adachi Mitsuru
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Int Arch Allergy Immunol. 2009;149 Suppl 1(Suppl 1):7-13. doi: 10.1159/000210647. Epub 2009 Jun 3.
Osteopontin (OPN) contributes to the development of T helper 1 (Th1)-mediated immunity and Th1-associated diseases. However, the role of OPN in bronchial asthma is unclear. Corticosteroids reduce airway inflammation, as reflected by the low eosinophil and T-cell counts, and the low level of cytokine expression. We investigated OPN production and the inhibitory effects of corticosteroids on OPN production in a murine model of allergic asthma.
BALB/c mice were sensitized by intraperitoneal injections of ovalbumin (OVA) with alum. Some mice received daily injections of dexamethasone (DEX) or phosphate-buffered saline for 1 week. All OVA-challenged mice were exposed to aerosolized 1% OVA for 30 min an hour after these injections. After the OVA challenge, the mice were killed, and bronchoalveolar lavage (BAL) fluid and lung tissue were examined.
The levels of OPN protein in BAL fluid and OPN mRNA in lung tissue increased after OVA challenge. Most OPN-expressing cells were CD11c+ cells and some were T cells. DEX decreased the levels of OPN protein in the BAL fluid, and those of OPN mRNA and OPN protein in lung tissue.
OPN may play an important role in allergic bronchial asthma. Corticosteroids inhibit OPN production in mice with allergic asthma. The beneficial effect of corticosteroids in bronchial asthma is partly due to their inhibitory effects on OPN production.
骨桥蛋白（OPN）有助于辅助性T细胞1（Th1）介导的免疫反应及Th1相关疾病的发展。然而，OPN在支气管哮喘中的作用尚不清楚。皮质类固醇可减轻气道炎症，表现为嗜酸性粒细胞和T细胞计数降低以及细胞因子表达水平降低。我们在过敏性哮喘小鼠模型中研究了OPN的产生以及皮质类固醇对OPN产生的抑制作用。
通过腹腔注射卵清蛋白（OVA）与明矾使BALB/c小鼠致敏。部分小鼠每日注射地塞米松（DEX）或磷酸盐缓冲盐水，持续1周。在这些注射1小时后，所有接受OVA激发的小鼠暴露于雾化的1%OVA中30分钟。OVA激发后，处死小鼠，检查支气管肺泡灌洗（BAL）液和肺组织。
OVA激发后，BAL液中OPN蛋白水平和肺组织中OPN mRNA水平升高。大多数表达OPN的细胞为CD11c+细胞，部分为T细胞。DEX降低了BAL液中OPN蛋白水平以及肺组织中OPN mRNA和OPN蛋白水平。
OPN可能在过敏性支气管哮喘中起重要作用。皮质类固醇抑制过敏性哮喘小鼠中OPN的产生。皮质类固醇在支气管哮喘中的有益作用部分归因于其对OPN产生的抑制作用。
