Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway
Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway
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DOI：
10.1016/j.bbrc.2006.09.117
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发表时间：
2006-11-24
影响因子：
3.1
通讯作者：
Kobayashi, Masashi
中科院分区：
文献类型：
--
作者：
Miyabayashi, Koutarou;Maruyama, Muneharu;Kobayashi, Masashi
据报道，β（2）-激动剂除了支气管扩张外，还可能发挥一些抗炎作用，这可能有助于其对哮喘控制的有益作用。众所周知，支气管上皮细胞通过产生可影响气道炎症的各种生物活性介质来响应一系列刺激。RANTES（regulated on activation，normal T cells expressed and secreted）通过其对嗜酸性粒细胞的趋化活性在哮喘气道炎症的病理生理学中起重要作用。在这项研究中，作者研究了β-激动剂异丙肾上腺素（ISO）是否可以调节BEAS-2B人支气管上皮细胞中的奎宁诱导的RANTES释放。c-jun N-末端激酶（JNK）通路的可能参与也进行了研究。肿瘤坏死因子-α和白细胞介素-1 β（细胞因子混合物）的组合增加了BEAS-2B细胞的RANTES释放，并刺激JNK活性。与JNK抑制剂SP 600125类似，ISO不仅抑制RANTES的产生，而且抑制细胞因子混合物刺激的BEAS-2B细胞中JNK通路的激活。ISO的作用是由β（2）-肾上腺素受体介导的，因为它被选择性β（2）-受体拮抗剂ICI 118，551阻断，但不被选择性β（1）-受体拮抗剂阿替洛尔阻断。腺苷酸环化酶激活剂毛喉素再现ISO的影响。发现异丙肾上腺素抑制RANTES从人支气管上皮细胞的释放。至少部分是通过抑制JNK信号通路。(c)2006年爱思唯尔公司All rights reserved.
It has been reported that beta(2)-agonists may potentially exert some anti-inflammatory action in addition to bronchodilation that may contribute to their beneficial effects on asthma control. Bronchial epithelial cells are well known to respond to a range of stimuli by producing various biologically active mediators that can influence airway inflammation. RANTES (regulated on activation, normal T cells expressed and secreted) plays an important role in the pathophysiology of airway inflammation of asthmatics through its chemotactic activity for eosinophils. In this study, the authors investigated whether cytokine-induced RANTES release from BEAS-2B human bronchial epithelial cells could be modulated by beta-agonist isoproterenol (ISO). The possible involvement of c-jun N-terminal kinase (JNK) pathway was also studied. Combination of tumor necrosis factor-alpha and interleukin-1 beta (cytokine mix) increased RANTES release from BEAS-2B cells, and stimulated JNK activity. Similar to JNK inhibitor SP600125, ISO inhibited not only the production of RANTES but also the activation of JNK pathway in cytokine mix-stimulated BEAS-2B cells. The effect of ISO was mediated by the beta(2)-adrenoceptor, since it was blocked by ICI 118,551, a selective beta(2)-receptor antagonist, but not by atenolol, a selective beta(1)-receptor antagonist. Adenylyl cyclase activator forskolin reproduced the effects of ISO. Isoproterenol was found to inhibit the release of RANTES from the human bronchial epithelial cells. at least in part, through the inhibition of JNK signaling pathway. (c) 2006 Elsevier Inc. All rights reserved.