Bailey K L, Poole J A, Mathisen T L, Wyatt T A, Von Essen S G, Romberger D J
Pulmonary, Critical Care, Sleep and Allergy Section, Deptartment of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5300, USA.
Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1049-54. doi: 10.1152/ajplung.00526.2007. Epub 2008 Mar 21.
Hog confinement workers are at high risk to develop chronic bronchitis as a result of their exposure to organic dust. Chronic bronchitis is characterized by inflammatory changes of the airway epithelium. A key mediator in inflammation is Toll-like receptor 2 (TLR2). We investigated the role of TLR2 in pulmonary inflammation induced by hog confinement dust. Normal human bronchial epithelial cells (NHBE) were grown in culture and exposed to hog confinement dust extract. Hog confinement dust upregulated airway epithelial cell TLR2 mRNA in a concentration- and time-dependent manner using real-time PCR. There was a similar increase in TLR2 protein at 48 h as shown by Western blot. TLR2 was upregulated on the surface of airway epithelial cells as shown by flow cytometry. A similar upregulation of pulmonary TLR2 mRNA and protein was shown in a murine model of hog confinement dust exposure. Hog confinement dust is known to stimulate epithelial cells to produce IL-6. To determine whether TLR2 expression was being regulated by IL-6, the production of IL-6 was blocked using an IL-6-neutralizing antibody. This resulted in attenuation of the dust-induced upregulation of TLR2. To further demonstrate the importance of IL-6 in the regulation of TLR2, NHBE were directly stimulated with recombinant human IL-6. IL-6 alone was able to upregulate TLR2 in airway epithelial cells. Hog confinement dust upregulates TLR2 in the airway epithelium through an IL-6-dependent mechanism.
由于接触有机粉尘，饲养场工人患慢性支气管炎的风险很高。慢性支气管炎的特征是气道上皮发生炎症变化。炎症中的一个关键介质是Toll样受体2（TLR2）。我们研究了TLR2在猪舍粉尘诱导的肺部炎症中的作用。将正常人支气管上皮细胞（NHBE）进行培养，并使其暴露于猪舍粉尘提取物中。使用实时PCR技术，猪舍粉尘以浓度和时间依赖性方式上调气道上皮细胞TLR2 mRNA。如蛋白质印迹法所示，48小时时TLR2蛋白也有类似的增加。流式细胞术显示气道上皮细胞表面的TLR2上调。在猪舍粉尘暴露的小鼠模型中也显示出肺部TLR2 mRNA和蛋白有类似的上调。已知猪舍粉尘会刺激上皮细胞产生IL-6。为了确定TLR2的表达是否受IL-6调节，使用IL-6中和抗体阻断IL-6的产生。这导致粉尘诱导的TLR2上调减弱。为了进一步证明IL-6在TLR2调节中的重要性，用重组人IL-6直接刺激NHBE。单独的IL-6就能上调气道上皮细胞中的TLR2。猪舍粉尘通过IL-6依赖机制上调气道上皮中的TLR2。
