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首页> 外文期刊>International Journal of Chronic Obstructive Pulmonary Disease >Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD
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Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD

机译：布地奈德对有无COPD吸烟者肺泡巨噬细胞toll样受体表达的影响

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Introduction: Alveolar macrophages (AMs) are equipped with innate immune receptors such as toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4). In primary bronchial epithelial cells, exposure of toll-like receptor (TLR) ligands or tumor necrosis factor-alpha (TNF-α) increased TLR2 mRNA expression and reduced interleukin-8 (IL-8) release when coincubated with glucocorticosteroids. The aim of this study was to compare TLR2 and TLR4 expression levels and the effect of a glucocorticosteroid after stimulation with TLR ligands on AMs from smokers with and without COPD compared with the healthy controls. Subjects and methods: Bronchoalveolar lavage was performed, and AMs were isolated from smokers with (n=10) and without COPD (n=11) and healthy controls (n=10) and stimulated ex vivo with peptidoglycan (PGN), lipopolysaccharide (LPS), or TNF-α ± budesonide (Bud). Blocking antibodies to TLR2 or TLR4 were added before stimulation with LPS or PGN ± Bud, respectively. The release of proinflammatory cytokine (TNF-α), chemoattractant (CXCL8), and TLR expression was analyzed by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Results: LPS, PGN, and TNF-α induced an increased release of IL-8 and TNF-α in the AMs in all the groups independent of smoking or disease. These responses were inhibited by a glucocorticosteroid (Bud) in all the three groups, except PGN-induced IL-8 secretion in smokers without COPD. Bud increased TLR2 expression in the healthy controls and smokers without COPD. Costimulation of TLR ligands and Bud significantly enhanced TLR2 mRNA expression in both groups of smokers compared with TLR ligands alone. In smokers, costimulation with PGN and Bud significantly increased TLR2 expression when compared with Bud alone. On stimulation with the TLR4 agonist, LPS downregulated TLR4 mRNA expression in all the three groups. Conclusion: The combination of glucocorticosteroids with TLR ligands can increase TLR2 expression, thereby improving host defense in smokers. Also this combination can decrease the secretion of proinflammatory cytokines and chemokines as an anti-inflammatory response. Our findings indicate that glucocorticosteroid therapy strengthens immune defense pathways, which may have implication during exacerbation caused by microorganisms.
机译：简介：肺泡巨噬细胞（AM）配备有先天性免疫受体，例如toll样受体2（TLR2）和toll样受体4（TLR4）。在原发性支气管上皮细胞中，与糖皮质激素共孵育时，通行费样受体（TLR）配体或肿瘤坏死因子-α（TNF-α）的暴露可增加TLR2 mRNA表达并减少白介素8（IL-8）释放。这项研究的目的是比较TLR2和TLR4的表达水平，以及与健康对照组相比，用TLR配体刺激后吸烟者在患有COPD和未患有COPD的吸烟者AMs上的作用。受试者和方法：进行了支气管肺泡灌洗，并从吸烟者（n = 10）和无COPD（n = 11）和健康对照组（n = 10）的吸烟者中分离出AM，并用肽聚糖（PGN），脂多糖（LPS）进行离体刺激）或TNF-α±布地奈德（Bud）。在分别用LPS或PGN±Bud刺激之前，先加入了针对TLR2或TLR4的封闭抗体。通过酶联免疫吸附试验和逆转录聚合酶链反应分析促炎细胞因子（TNF-α），趋化因子（CXCL8）和TLR表达的释放。结果：LPS，PGN和TNF-α诱导了所有独立于吸烟或疾病的组中AMs中IL-8和TNF-α的释放增加。除PGN诱导无COPD吸烟者的IL-8分泌外，三组中的这些反应均受到糖皮质激素（Bud）的抑制。芽增加健康对照者和无COPD吸烟者中TLR2的表达。与单独的TLR配体相比，两组吸烟者中TLR配体和芽的共刺激显着增强了TLR2 mRNA的表达。在吸烟者中，与单独的Bud相比，与PGN和Bud的共刺激显着增加TLR2表达。在TLR4激动剂刺激下，LPS在所有三组中均下调了TLR4 mRNA表达。结论：糖皮质激素与TLR配体结合可以增加TLR2的表达，从而改善吸烟者的宿主防御能力。同样，这种组合可以减少促炎细胞因子和趋化因子的分泌，作为一种抗炎反应。我们的研究结果表明，糖皮质激素治疗可增强免疫防御途径，这可能在微生物加重期间具有一定的意义。

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