Lane Andrew P, Truong-Tran Quynh Ai, Schleimer Robert P
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Am J Rhinol. 2006 Mar-Apr;20(2):138-44.
The role of the innate immune system in the pathophysiology of chronic rhinosinusitis (CRS) is poorly understood. In this study, we compared sinonasal expression of toll-like receptors (TLRs), complement components, serum amyloid A, and inflammatory genes (chemokines and cytokines) in control subjects and patients undergoing sinus surgery for CRS.
Eleven control subjects and 30 subjects with CRS unresponsive to medical management were enrolled prospectively before undergoing endoscopic sinus surgery. Ethmoid mucosal specimens were obtained surgically and processed for RNA extraction. Real-time polymerase chain reaction was used to quantitate the level of expression of messenger RNA (mRNA) for TLR, acute phase proteins, and cytokine genes. Subjects were followed for a minimum of 6 months postoperatively with nasal endoscopy to assess for recurrence of polyps.
mRNA for all target genes was detected in the ethmoid mucosa of both control and CRS subjects. The level of gene expression was normalized to the housekeeping genes 18s RNA and glyceraldehyde-3-phosphate dehydrogenase. As compared with controls, CRS was associated with significantly higher expression of TLR2 and the inflammatory genes macrophage-inflammatory protein alpha, RANTES, and granulocyte-macrophage colony-stimulating factor. Patients with early recurrence of polyps after surgery had significantly decreased expression of TLR2, 9, and serum amyloid A and increased expression of macrophage-inflammatory protein alpha compared with surgery-responsive patients.
This study shows the increased levels of expression of TLR2 and a variety of inflammatory genes in sinonasal mucosa of CRS patients compared with controls. Whether these differences play a role in pathogenesis or are merely manifestations of disease activity is worthy of investigation.
先天性免疫系统在慢性鼻-鼻窦炎（CRS）病理生理学中的作用尚不清楚。在本研究中，我们比较了对照组与接受CRS鼻窦手术患者鼻窦中Toll样受体（TLR）、补体成分、血清淀粉样蛋白A及炎症基因（趋化因子和细胞因子）的表达。
前瞻性纳入11名对照受试者和30名药物治疗无效的CRS受试者，在接受鼻内镜鼻窦手术前进行研究。通过手术获取筛窦黏膜标本并进行RNA提取。采用实时聚合酶链反应定量检测TLR、急性期蛋白及细胞因子基因的信使核糖核酸（mRNA）表达水平。术后至少随访6个月，通过鼻内镜评估息肉复发情况。
在对照组和CRS受试者的筛窦黏膜中均检测到所有靶基因的mRNA。基因表达水平以内参基因18s RNA和甘油醛-3-磷酸脱氢酶进行标准化。与对照组相比，CRS患者中TLR2及炎症基因巨噬细胞炎性蛋白α、调节激活正常T细胞表达和分泌因子（RANTES）、粒细胞-巨噬细胞集落刺激因子的表达显著升高。术后息肉早期复发的患者与手术有效患者相比，TLR2、9及血清淀粉样蛋白A的表达显著降低，巨噬细胞炎性蛋白α的表达升高。
本研究表明，与对照组相比，CRS患者鼻窦黏膜中TLR2及多种炎症基因的表达水平升高。这些差异是在发病机制中发挥作用还是仅仅为疾病活动的表现，值得进一步研究。
