Division of Pharmacology and Pathophysiology Utrecht Institute for Pharmaceutical Sciences Faculty of Sciences, Utrecht University, PO BOX 80082, 3508 TB Utrecht, The Netherlands.
Eur Respir J. 2010 Nov;36(5):1143-54. doi: 10.1183/09031936.00062209. Epub 2009 Oct 19.
Chronic obstructive pulmonary disease (COPD) is a major health problem and cigarette smoke is the main risk factor for the development of COPD. The characteristic changes in airway morphology, inflammatory cell infiltration and mediator expression in COPD may result from direct effects of cigarette smoke on airway cells. Toll-like receptors (TLRs) are key elements in pathogen recognition by the host immune system. Although TLRs have been intensely studied in innate immunity and infection, their critical role in noninfectious challenges has only recently emerged. Here we investigate whether cigarette smoke induces TLR9 signalling in human neutrophils. Human neutrophils were isolated from buffy coat and exposed to cigarette smoke extract. The production of CXC chemokine ligand (CXCL)8 was measured as a functional readout and the role of TLR9 signalling was investigated. Cigarette smoke extract induced CXCL8 release via TLR9 activation in neutrophils, which was confirmed in TLR9 stably transfected human embryonic kidney 293 cells. Moreover, cigarette smoke extract upregulated the expression of TLR9 and the upregulated expression was suppressed by N-acetylcysteine. TLR9 mediates cigarette smoke-induced release of CXCL8 and this may contribute to the accumulation of neutrophils and inflammation within the airways of smokers.
慢性阻塞性肺疾病（COPD）是一个主要的健康问题，香烟烟雾是 COPD 发展的主要危险因素。COPD 气道形态学、炎症细胞浸润和介质表达的特征性变化可能是由于香烟烟雾对气道细胞的直接作用所致。Toll 样受体（TLR）是宿主免疫系统识别病原体的关键因素。尽管 TLR 在先天免疫和感染方面已经得到了深入研究，但它们在非传染性挑战中的关键作用直到最近才显现出来。在这里，我们研究了香烟烟雾是否会诱导人中性粒细胞中的 TLR9 信号转导。我们从白细胞层中分离出人中性粒细胞，并将其暴露于香烟烟雾提取物中。以 CXC 趋化因子配体（CXCL）8 的产生作为功能读数来测量，并研究了 TLR9 信号转导的作用。香烟烟雾提取物通过 TLR9 激活诱导中性粒细胞中 CXCL8 的释放，这在 TLR9 稳定转染的人胚肾 293 细胞中得到了证实。此外，香烟烟雾提取物上调了 TLR9 的表达，而 N-乙酰半胱氨酸抑制了上调的表达。TLR9 介导香烟烟雾诱导的 CXCL8 释放，这可能导致吸烟者气道中中性粒细胞的积累和炎症。
