Role of thrombin in chronic rhinosinusitis-associated tissue remodeling
Role of thrombin in chronic rhinosinusitis-associated tissue remodeling
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DOI：
10.2500/ajra.2011.25.3535
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发表时间：
2011-01-01
影响因子：
2.6
通讯作者：
Shimizu, Takeshi
中科院分区：
文献类型：
--
作者：
Shimizu, Shino;Gabazza, Esteban C.;Shimizu, Takeshi
背景资料：凝血酶是凝血系统的效应酶，其蛋白酶激活受体（PARs）可促进鼻部疾病的炎症反应。慢性鼻窦炎（CRS）的特征是细胞外基质蛋白沉积增加，组织重塑和鼻息肉形成。凝血酶在慢性鼻炎症相关组织重塑中的作用尚未得到评价。方法：收集CRS伴鼻息肉（CRSwNP）伴哮喘（n = 9）、CRSwNP不伴哮喘（n = 10）、过敏性鼻炎（n = 7）和对照组（n = 3）患者的鼻分泌物，探讨凝血酶在CRS发病机制中的作用。凝血酶，凝血酶-抗凝血酶（达特）复合物，和血管内皮生长因子（VEGF）的浓度进行了评价，通过酶免疫分析。测定各组患者鼻分泌物中凝血酶和达特复合物的浓度，并测定经凝血酶或凝血酶受体激动剂肽处理的气道上皮细胞培养液中VEGF的浓度。结果：与对照组相比，CRSwNPs哮喘患者鼻分泌物中凝血酶和达特复合物显著增加。凝血酶和PAR-1激动剂肽显着刺激VEGF分泌从培养的人气道上皮cells.Conclusion：本研究的结果表明，有增加激活的凝血系统在鼻粘膜的CRS患者和凝血酶可能发挥作用，鼻息肉形成刺激VEGF生产从气道上皮细胞。(Am J Rhinol Allergy 25，7-11，2011; doi：10.2500/ajra.2011.25.3535）
Background: Thrombin, the effector enzyme of the coagulation system, has been reported to promote inflammatory responses in nasal diseases through its protease-activated receptors (PARs). Chronic rhinosinusitis (CRS) is characterized by increased deposition of extracellular matrix proteins, tissue remodeling, and formation of nasal polyps. The role of thrombin in chronic nasal inflammation-associated tissue remodeling still has not been appraised. This study was conducted to elucidate the role of thrombin in the pathogenesis of CRS.Methods: Nasal secretion was collected from patients with CRS with nasal polyp (CRSwNP) with asthma (n = 9), CRSwNP without asthma (n = 10), allergic rhinitis (n = 7), and control patients (n = 3). The concentrations of thrombin, thrombin-antithrombin (TAT) complex, and vascular endothelial growth factor (VEGF) were evaluated by enzyme immunoassays. The concentration of thrombin and TAT complex was measured in nasal secretion from each group of patients, and VEGF was measured in culture medium from airway epithelial cells treated with thrombin or thrombin receptor agonist peptide.Results: Thrombin and TAT complex were significantly increased in nasal secretion of patients with CRSwNPs with asthma compared with the control group. Thrombin and PAR-1 agonist peptide significantly stimulated VEGF secretion from cultured human airway epithelial cells.Conclusion: The results of this study showed that there is increased activation of the coagulation system in the nasal mucosa of CRS patients and that thrombin may play a role in nasal polyp formation by stimulating VEGF production from airway epithelial cells. (Am J Rhinol Allergy 25, 7-11, 2011; doi: 10.2500/ajra.2011.25.3535)