Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Pediatr Allergy Immunol. 2010 Mar;21(2 Pt 1):345-52. doi: 10.1111/j.1399-3038.2009.00906.x. Epub 2009 Dec 7.
Eotaxin-1 (CCL11), an eosinophil-specific C-C chemokine, is a potent chemoattractant for mobilization of eosinophils into airways after allergic stimulation. Eotaxin-1 recruits eosinophils into inflammatory sites, and may play a role in the pathogenesis of asthma. Formoterol and salmeterol are two inhaled long acting beta(2) adrenoceptor agonists (LABAs), widely used for the local treatment of asthma. However, little is known about their effects on the eotaxin-1 expression of bronchial epithelial cells. BEAS-2B cells were stimulated by adding IL-4 with or without 2 h pre-treatment of formoterol or salmeterol. The protein and mRNA expression of eotaxin-1 were measured by ELISA assay and real-time PCR, respectively. Effects of formoterol and salmeterol on nuclear and cytosolic pSTAT-6 expression were evaluated by Western blot and immunofluorescence study. Formoterol and salmeterol (10(-7)-10(-10) m) significantly down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. A specific beta(2) adrenoceptor antagonist (ICI 118,551) reversed their suppression of eotaxin-1 production. Forskolin, an cAMP activator, could also suppress the expression of eotaxin-1 by IL-4 in a dose dependent manner (10(-7)-10(-10 )m). The western blot and immunofluorescence studies demonstrated that formoterol 10(-7 )m suppressed the nuclear expression of pSTAT-6. Formoterol and salmeterol, two inhaled long-acting beta(2) agonists, down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. The effect was mediated via the beta(2) adrenoceptor, and cAMP. Formoterol significantly down-regulated pSTAT6 at higher concentration, and further turned off the IL-4 signaling pathway.
嗜酸性粒细胞趋化蛋白-1（CCL11）是一种嗜酸性粒细胞特异性的 C-C 趋化因子，是变应原刺激后将嗜酸性粒细胞募集到气道中的一种有效的趋化因子。嗜酸性粒细胞趋化蛋白-1 募集嗜酸性粒细胞到炎症部位，并可能在哮喘发病机制中发挥作用。福莫特罗和沙美特罗是两种吸入性长效β2 肾上腺素受体激动剂（LABAs），广泛用于局部治疗哮喘。然而，关于它们对支气管上皮细胞嗜酸性粒细胞趋化蛋白-1 表达的影响知之甚少。用 IL-4 刺激 BEAS-2B 细胞，或先用福莫特罗或沙美特罗预处理 2 小时后再用 IL-4 刺激 BEAS-2B 细胞。通过 ELISA 测定和实时 PCR 分别测量嗜酸性粒细胞趋化蛋白-1 的蛋白和 mRNA 表达。通过 Western blot 和免疫荧光研究评估福莫特罗和沙美特罗对核和胞质 pSTAT-6 表达的影响。福莫特罗和沙美特罗（10(-7)-10(-10) m）显著下调 IL-4 诱导的 BEAS-2B 细胞中嗜酸性粒细胞趋化蛋白-1 的表达。β2 肾上腺素受体特异性拮抗剂（ICI 118,551）逆转了它们对嗜酸性粒细胞趋化蛋白-1 产生的抑制作用。forskolin，一种 cAMP 激活剂，也可以以剂量依赖的方式抑制 IL-4 诱导的嗜酸性粒细胞趋化蛋白-1 的表达（10(-7)-10(-10) m）。Western blot 和免疫荧光研究表明，福莫特罗 10(-7) m 抑制了核内 pSTAT-6 的表达。福莫特罗和沙美特罗，两种吸入性长效β2 激动剂，下调了 BEAS-2B 细胞中 IL-4 诱导的嗜酸性粒细胞趋化蛋白-1 的表达。该作用通过β2 肾上腺素受体和 cAMP 介导。福莫特罗在较高浓度下显著下调 pSTAT6，并进一步关闭了 IL-4 信号通路。
