Wang J H, Devalia J L, Sapsford R J, Davies R J
Academic Dept of Respiratory Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, UK.
Eur Respir J. 1997 Apr;10(4):834-40.
We have recently demonstrated that human bronchial epithelial cells can synthesise and release several inflammatory mediators, including the factor regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble intercellular adhesion molecule-1 (sICAM-1), which influence the activity of eosinophils, and may, therefore play a role in the aetiology of asthma. In this study we investigated whether corticosteroids could influence the release of these proinflammatory mediators from human bronchial epithelial cells. Human bronchial epithelial cells were cultured to confluence as explant cultures, and incubated in the presence of 50 ng x mL(-1) tumour necrosis factor-alpha (TNF-alpha) +/- 0-10(-4) M of either fluticasone propionate (FP), beclomethasone dipropionate (BDP), or hydrocortisone (HC) for 24 h. The culture medium was collected and analyzed for RANTES and sICAM-1, by enzyme-linked immunosorbent assay (ELISA), and the cells were analysed for total protein. The TNF-alpha significantly increased the release both of RANTES and sICAM-1 (63.0 fg RANTES x microg(-1) protein; p<0.05; 8.8 pg sICAM-1 x microg(-1) protein; p<0.02), when compared with untreated cells (10.3 fg RANTES x microg(-1) protein; 2.6 pg sICAM-1 x microg(-1) cellular protein). The TNF-alpha-induced release both of RANTES and sICAM-1 occurred in a time-dependent manner, and was maximal by 24 h incubation. FP 10(-6)-10(-4) M significantly attenuated the TNF-alpha-induced release both of RANTES and sICAM-1. In contrast, 10(-4) M BDP or HC significantly attenuated the release of only sICAM-1. These results suggest that corticosteroids may prevent airway inflammation by downregulating the synthesis and/or release of proinflammatory mediators from bronchial epithelial cells. Furthermore, fluticasone propionate may be more efficacious than beclomethasone dipropionate or hydrocortisone in this respect.
我们最近证实，人支气管上皮细胞能够合成并释放多种炎症介质，包括激活调节正常T细胞表达和分泌因子（RANTES）以及可溶性细胞间黏附分子-1（sICAM-1），这些介质会影响嗜酸性粒细胞的活性，因此可能在哮喘的病因学中发挥作用。在本研究中，我们调查了皮质类固醇是否会影响人支气管上皮细胞释放这些促炎介质。将人支气管上皮细胞培养至汇合状态作为外植体培养物，并在存在50 ng·mL⁻¹肿瘤坏死因子-α（TNF-α）±0.1×10⁻⁴ M的丙酸氟替卡松（FP）、二丙酸倍氯米松（BDP）或氢化可的松（HC）的情况下孵育24小时。收集培养基并通过酶联免疫吸附测定（ELISA）分析其中的RANTES和sICAM-1，并分析细胞中的总蛋白。与未处理的细胞（RANTES为10.3 fg·μg⁻¹蛋白；sICAM-1为2.6 pg·μg⁻¹细胞蛋白）相比，TNF-α显著增加了RANTES和sICAM-1的释放（RANTES为63.0 fg·μg⁻¹蛋白；p<0.05；sICAM-1为8.8 pg·μg⁻¹蛋白；p<0.02）。TNF-α诱导的RANTES和sICAM-1释放呈时间依赖性，在孵育24小时时达到最大值。10⁻⁶ - 10⁻⁴ M的FP显著减弱了TNF-α诱导的RANTES和sICAM-1释放。相比之下，10⁻⁴ M的BDP或HC仅显著减弱了sICAM-1的释放。这些结果表明，皮质类固醇可能通过下调支气管上皮细胞促炎介质的合成和/或释放来预防气道炎症。此外，在这方面，丙酸氟替卡松可能比二丙酸倍氯米松或氢化可的松更有效。
