Wolf Lisa, Sapich Sandra, Honecker Anja, Jungnickel Christopher, Seiler Frederik, Bischoff Markus, Wonnenberg Bodo, Herr Christian, Schneider-Daum Nicole, Lehr Claus-Michael, Bals Robert, Beisswenger Christoph
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany; and.
Am J Physiol Lung Cell Mol Physiol. 2016 Nov 1;311(5):L1015-L1022. doi: 10.1152/ajplung.00158.2016. Epub 2016 Sep 30.
Lung epithelial cells are suggested to promote pathogen-induced pulmonary inflammation by the release of chemokines, resulting in enhanced recruitment of circulating leukocytes. Recent studies have shown that the interleukin-17C (IL-17C) regulates innate immune functions of epithelial cells in an autocrine manner. The aim of this study was to investigate the contribution of IL-17C to pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL-17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression of the neutrophil-recruiting chemokines keratinocyte-derived chemokine and macrophage inflammatory protein 2 were significantly decreased in lungs of IL-17C-deficient (IL-17C) mice infected with P. aeruginosa at 24 h. Systemic concentrations of interleukin-6 (IL-6) were significantly decreased in infected IL-17C mice at 24 h and the survival of IL-17C mice was significantly increased at 48 h. The expression of IL-17C was reduced in infected mice deficient for interleukin-17A (IL-17A), whereas pulmonary concentrations of IL-17A were not affected by the deficiency for IL-17C. Stimulation of primary alveolar epithelial cells with IL-17A resulted in a significantly increased expression of IL-17C in vitro. Our data suggest that IL-17A-mediated expression of epithelial IL-17C amplifies the release of chemokines by epithelial cells and thereby contributes to the recruitment of neutrophils and systemic inflammation during acute P. aeruginosa pneumonia.
肺上皮细胞被认为可通过释放趋化因子促进病原体诱导的肺部炎症，从而增强循环白细胞的募集。最近的研究表明，白细胞介素17C（IL-17C）以自分泌方式调节上皮细胞的固有免疫功能。本研究的目的是在急性铜绿假单胞菌肺炎小鼠模型中研究IL-17C对肺部炎症的作用。铜绿假单胞菌感染导致野生型小鼠肺组织中IL-17C表达增加。在感染铜绿假单胞菌24小时时，IL-17C缺陷（IL-17C-/-）小鼠肺中的中性粒细胞数量以及中性粒细胞募集趋化因子角质形成细胞衍生趋化因子和巨噬细胞炎性蛋白2的表达显著降低。感染的IL-17C-/-小鼠在24小时时白细胞介素6（IL-6）的全身浓度显著降低，且IL-17C-/-小鼠在48小时时的存活率显著提高。在白细胞介素17A（IL-17A）缺陷的感染小鼠中，IL-17C的表达降低，而肺中IL-17A的浓度不受IL-17C缺陷的影响。用IL-17A刺激原代肺泡上皮细胞导致体外IL-17C的表达显著增加。我们的数据表明，IL-17A介导的上皮IL-17C表达放大了上皮细胞趋化因子的释放，从而在急性铜绿假单胞菌肺炎期间有助于中性粒细胞的募集和全身炎症反应。
