Inflammation and remodelling patterns in early stage chronic rhinosinusitis
Inflammation and remodelling patterns in early stage chronic rhinosinusitis
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DOI：
10.1111/j.1365-2222.2011.03898.x
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发表时间：
2012-06-01
影响因子：
6.1
通讯作者：
Bachert, C.
中科院分区：
文献类型：
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作者：
Van Bruaene, N.;Perez-Novo, C.;Bachert, C.
目的研究慢性鼻窦炎（CRSsNP）患者早期鼻窦黏膜中炎症因子和重塑因子的表达，为揭示CRSsNP的早期发病机制提供理论依据。取筛泡和后筛窦，测定TGF-β 1及其受体、MPO蛋白以及促炎细胞因子（TNF-α和IL-1 β）和Th 1细胞标志（IFN-γ和T-bet）。作为TGF-β信号传导的结果参数，分析胶原沉积。结果TGF-β 1蛋白在上颌窦中的表达明显升高，在上颌窦中的表达与正常对照组相比无显著性差异（P = 0.006），钩突（P = 0.01），前筛窦包括筛泡（P = 0.005）和后筛窦（P = 0.037）与下、中鼻甲比较。胶原沉积显着增加上颌窦相比，下鼻甲（P = 0.008）。相比之下，TGF-β受体、Th 1相关标志物（IFN-γ和T-bet）、促炎细胞因子（IL-1 β和TNF-α）和作为中性粒细胞标志物的MPO蛋白的mRNA在所有位置均有表达，但在不同位置之间没有显示出显著差异。CRSsNP患者下鼻甲中TGF-β 1 mRNA的表达显著高于对照组（P = 0.017）。促炎性细胞因子和Th 1相关细胞因子没有表现出上调CRSsNP下鼻甲时，相比controls.Conclusions在早期阶段的慢性鼻窦疾病，TGF-β蛋白的表达在鼻窦内的浓度显着较高时，相比，鼻甲，而促炎性，嗜中性粒细胞和Th 1标志物没有表现出任何差异。这些发现表明，TGF-β在CRSsNP的启动中起着核心作用，并代表了进一步研究和未来干预的主要目标。
Background A distinct set of inflammatory and remodelling factors have been found elevated in chronic rhinosinusitis.Objective The investigation of their expression in early stage disease may reveal early events in this common disease.Methods Sinonasal mucosal samples from nine patients with early stage CRSsNP were taken from the inferior and middle turbinates, the uncinate process, maxillary sinus, anterior ethmoid, bulla ethmoidalis and the posterior ethmoid and measured for TGF-beta 1 and it's receptors, MPO protein as well as pro-inflammatory cytokines (TNF-alpha and IL-1beta) and the Th1 cell signature (IFN-gamma and T-bet). As outcome parameter for TGF-beta signalling collagen deposition was analysed. Inferior turbinates from patients undergoing (rhino-) septoplasty were collected as controls.Results TGF-beta 1 protein concentrations were significantly increased in the maxillary sinuses (P = 0.006), the uncinate process (P = 0.01), the anterior ethmoid including the bulla ethmoidalis (P = 0.005) and the posterior ethmoid (P = 0.037) when compared to the inferior and middle turbinates. Collagen deposition was significantly increased in the maxillary sinus when compared to the inferior turbinates (P = 0.008). In contrast, mRNA for TGF-beta receptors, Th1 related markers (IFN-gamma and T-bet), pro-inflammatory cytokines (IL-1 beta and TNF-alpha), and MPO protein as neutrophil marker were expressed at all locations but showed no significant differences between the various locations. TGF-beta 1 mRNA expression in inferior turbinates of CRSsNP was significantly higher when compared to inferior turbinates of controls (P = 0.017). The pro-inflammatory cytokines and Th1-related cytokines did not show an upregulation in inferior turbinates of CRSsNP when compared to controls.Conclusions In early stage chronic sinus disease, TGF-beta protein is expressed in significantly higher concentrations within the paranasal sinuses when compared to turbinates, whereas pro-inflammatory, neutrophilic and Th1 markers did not show any difference. These findings suggest that TGF-beta plays a central role in the initiation of CRSsNP, and represents a major target for further research and future intervention.