1 Unit for Lung and Airway Research, Institute of Environmental Medicine.
Am J Respir Crit Care Med. 2014 Nov 1;190(9):1022-31. doi: 10.1164/rccm.201404-0689OC.
The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known.
To characterize the role of IL-26 in antibacterial host defense of human lungs.
Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro.
Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells.
This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.
Th17 细胞因子 IL-26 在肺部的抗菌宿主防御中的作用尚不清楚。
阐明 IL-26 在人体肺部抗菌宿主防御中的作用。
支气管镜检查时，向健康志愿者的支气管内给予内毒素和载体，然后采集支气管肺泡灌洗液（BAL）样本。采用免疫细胞化学和免疫细胞荧光法检测细胞内 IL-26。还采用流式细胞术检测 IL-26 及其受体复合物。采用 ELISA 法检测细胞因子和磷酸化信号转导子和转录激活子（STAT）1 加 STAT3。采用实时聚合酶链反应分析基因表达，体外评估中性粒细胞迁移。
在没有体内预先暴露的情况下，BAL 样本中检测到细胞外 IL-26，内毒素暴露后明显增加。肺泡巨噬细胞显示出 IL-26 的基因表达、包含和释放。Th 和细胞毒性 T 细胞也含有 IL-26。在 BAL 样本中，IL-26 浓度与固有效应细胞呈相关性。重组 IL-26 增强了由 IL-8 和 fMLP 诱导的中性粒细胞趋化作用，但减少了中性粒细胞的趋化运动。条件培养基中中性粒细胞的髓过氧化物酶减少。IL-26 受体复合物在中性粒细胞中被检测到，IL-26 减少了这些细胞中磷酸化 STAT3。在 BAL 和支气管上皮细胞中，IL-26 增加了 IL-26 受体复合物和 STAT1 加 STAT3 的基因表达。最后，IL-26 增加了 BAL 中中性粒细胞动员细胞因子的释放，但在上皮细胞中没有增加。
本研究表明，肺泡巨噬细胞产生 IL-26，刺激人肺中中性粒细胞上的受体，并将其募集集中于细菌和积累的免疫细胞。
