Corticosteroid enhances TNF-α-mediated leukocyte adhesion to pulmonary microvascular endothelial cells
Corticosteroid enhances TNF-α-mediated leukocyte adhesion to pulmonary microvascular endothelial cells
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DOI：
10.1111/j.1398-9995.2008.01775.x
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发表时间：
2008-12-01
期刊：
影响因子：
12.4
通讯作者：
Saito, H.
中科院分区：
文献类型：
--
作者：
Matsuda, A.;Orihara, K.;Saito, H.
一些严重哮喘患者的特征是肿瘤坏死因子α（TNF-α）水平升高和气道中性粒细胞炎症。尽管哮喘的这种表型变化可能导致皮质类固醇无效，但 TNF-α 在此过程中的作用仍不清楚。 TNF-α主要通过作用于血管内皮来发挥其生物学作用，从而上调白细胞募集到发炎组织中。本研究的目的是在体外研究地塞米松（DEX）对来自肺血管的人微血管内皮细胞（HMVEC-LB1）的TNF-α介导的反应的影响。在存在和不存在DEX的情况下将HMVEC-LB1与TNF-α一起培养。测定了 DEX 对 TNF-α 介导的各种反应的影响，例如趋化因子和细胞粘附分子的表达、白细胞粘附。TNF-α 显着诱导生长相关癌基因 α (GRO-α)、白细胞介素 8 (IL-8)、调节激活、正常 T 细胞表达和分泌 (RANTES) 和干扰素诱导蛋白 10 (IP-10) 的产生以及细胞内粘附分子的细胞表面表达HMVEC-LB1上的ICAM-1(ICAM-1)和血管细胞粘附分子1(VCAM-1)。 DEX 处理可轻微减弱 TNF-α 诱导的 GRO-α 和 IL-8（分别达到 89% 和 79%），而相同处理后 IP-10、ICAM-1 和 VCAM-1 的表达显着增强（分别高达 172%、152% 和 139%）。相应地，DEX显着增强了嗜酸性粒细胞和中性粒细胞对TNF-α处理的HMVEC-LB1的体外粘附。在TNF-α介导的肺微血管内皮细胞的体外反应中发现了DEX（一种皮质类固醇）的一些促炎作用，即趋化因子的产生和白细胞粘附。这些体外结果至少可以部分解释严重哮喘患者中皮质类固醇的无效性伴随着 TNF-α 产生的显着增加。
Some severe asthma patients are characterized by elevated levels of tumor necrosis factor alpha (TNF-alpha) and neutrophilic inflammation in the airways. Although such phenotypic changes in asthma might contribute to corticosteroid refractoriness, the role of TNF-alpha in the process remains unclear. TNF-alpha exerts its biological effects mainly by acting on the vascular endothelium, and thereby upregulates leukocyte recruitment into inflamed tissues. The aim of this study was to investigate the effects of dexamethasone (DEX) on the TNF-alpha-mediated responses of human microvascular endothelial cells from lung blood vessels (HMVEC-LBl) in vitro.HMVEC-LBl were cultured with TNF-alpha in the presence and absence of DEX. The effects of DEX on various TNF-alpha-mediated responses, such as the expressions of chemokines and cellular adhesion molecules, leukocyte adhesion were determined.TNF-alpha significantly induced growth-related oncogene alpha (GRO-alpha), interleukin 8 (IL-8), regulated on activation, normal T-cell expressed and secreted (RANTES) and interferon-inducible protein 10 (IP-10) productions and cell surface expressions of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on HMVEC-LBl. TNF-alpha-induced GRO-alpha and IL-8 were slightly attenuated by DEX treatment (reaches to 89% and 79%, respectively), whereas expressions of IP-10, ICAM-1 and VCAM-1 were significantly enhanced by the same treatment (up to 172%, 152% and 139%, respectively). Correspondingly, in vitro adhesion of eosinophils and neutrophils to TNF-alpha-treated HMVEC-LBl were significantly enhanced by DEX.Some proinflammatory effects of DEX, a corticosteroid, were found in TNF-alpha-mediated in vitro reactions of pulmonary microvascular endothelial cells, i.e. chemokine productions and leukocyte adhesion. These in vitro results may explain, at least in part, the corticosteroid refractoriness accompanied by a marked increase in TNF-alpha production that is seen in severe asthmatic patients.