Kurokawa Masatsugu, Kokubu Fumio, Matsukura Satoshi, Kawaguchi Mio, Ieki Koushi, Suzuki Shintarou, Odaka Miho, Watanabe Shin, Takeuchi Hiroko, Akabane Tomoko, Asano Kazuhito, Iwase Michiko, Honma Ikuo, Adachi Mitsuru
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Int Arch Allergy Immunol. 2005;137 Suppl 1:60-8. doi: 10.1159/000085434. Epub 2005 Jun 2.
Thymus and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically attracts T-helper (Th) 2 cells positive for the CC chemokine receptor 4 (CCR4(+)). Corticosteroids reduce airway inflammation, as reflected by reduced numbers of eosinophils and T cells and reduced expression of cytokines. We investigated TARC production and the inhibitory effects of corticosteroids on TARC expression in a murine model of allergic asthma.
BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) with alum. Once daily for 1 week, mice received injections of dexamethasone or 0.2 ml saline (control), then 1 h later inhaled aerosolized 1% OVA for 30 min. Mice were killed 24 h after OVA challenge for bronchoalveolar lavage and lung tissue examination.
TARC was expressed mainly in the bronchial epithelial cells. Dexamethasone attenuated OVA-induced airway eosinophilia, lymphocyte infiltration, and airway hyperresponsiveness. Dexamethasone also decreased TARC production in the bronchoalveolar lavage fluid and decreased expression of TARC mRNA and TARC protein in lung tissue.
The corticosteroid dexamethasone inhibits TARC production in a murine model of allergic asthma in vivo. The beneficial effect of corticosteroids in bronchial asthma is due in part to their direct inhibitory effects on TARC production.
胸腺与活化调节趋化因子（TARC；CCL17）是一种淋巴细胞趋化性CC趋化因子，可特异性吸引对CC趋化因子受体4呈阳性（CCR4(+)）的辅助性T（Th）2细胞。皮质类固醇可减轻气道炎症，表现为嗜酸性粒细胞和T细胞数量减少以及细胞因子表达降低。我们在过敏性哮喘小鼠模型中研究了TARC的产生以及皮质类固醇对TARC表达的抑制作用。
通过腹腔注射卵清蛋白（OVA）与明矾使BALB/c小鼠致敏。小鼠连续1周每天接受地塞米松或0.2 ml生理盐水（对照）注射，然后1小时后吸入雾化的1%OVA 30分钟。OVA激发后24小时处死小鼠，进行支气管肺泡灌洗和肺组织检查。
TARC主要在支气管上皮细胞中表达。地塞米松减轻了OVA诱导的气道嗜酸性粒细胞增多、淋巴细胞浸润和气道高反应性。地塞米松还降低了支气管肺泡灌洗液中TARC的产生，并降低了肺组织中TARC mRNA和TARC蛋白的表达。
皮质类固醇地塞米松在体内过敏性哮喘小鼠模型中抑制TARC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它们对TARC产生的直接抑制作用。
