Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis.
Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis.
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DOI：
10.1016/j.jaci.2013.04.005
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Kato A
中科院分区：
文献类型：
--
作者：
Nagarkar DR;Poposki JA;Tan BK;Comeau MR;Peters AT;Hulse KE;Suh LA;Norton J;Harris KE;Grammer LC;Chandra RK;Conley DB;Kern RC;Schleimer RP;Kato A
慢性鼻-鼻窦炎合并鼻息肉(CRSwNP)与Th2为主的炎症有关。胸腺基质淋巴生成素(TSLP)是一种细胞因子，可触发树突状细胞介导的Th2炎症反应，并增强肥大细胞中IL-1依赖的Th2细胞因子的产生。尽管在鼻息肉中发现了TSLP基因的高水平表达，但TSLP蛋白在鼻息肉中的表达及其功能尚未得到充分的研究。本研究的目的是探讨TSLP在CRS中的作用。我们用ELISA法和Western印迹法研究了TSLP蛋白在NPs中的存在和稳定性，并用基于人肥大细胞激活的生物测定方法研究了TSLP在鼻腔组织提取物中的功能。虽然CRSwNP患者NP组织中TSLP基因的表达显著高于CRS患者和对照组钩状组织中的TSLP mRNA，但商品化的酶联免疫吸附试验检测到NP组织中的TSLP蛋白水平显著降低。我们发现NP提取物对重组TSLP的降解具有时间依赖性，并且这种降解被一种蛋白酶抑制剂鸡尾酒完全抑制，这表明TSLP对组织蛋白酶是敏感的。有趣的是，NP提取物处理的TSLP在肥大细胞中具有更高的活性，尽管全长TSLP的数量减少了85%。与钩状组织匀浆相比，NP提取物显著增强肥大细胞IL-1β依赖的IL-5的产生，并被抗TSLP显著抑制，提示NP含有与生物学相关的TSLP活性水平。TSLP及其代谢产物可能在CRSwNP的炎症反应中起重要作用。
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with Th2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated Th2 inflammatory responses and that enhances IL-1-dependent Th2 cytokine production in mast cells. Although elevated levels of TSLP mRNA have been found in nasal polyps (NPs), expression of TSLP protein and its function in CRS have not been fully explored. The objective of this study was to investigate the role of TSLP in CRS. We investigated the presence and stability of TSLP protein in NPs by ELISA and western blot, and the function of TSLP in nasal tissue extracts with a bioassay based upon activation of human mast cells. Although TSLP mRNA was significantly increased in NP tissue from patients with CRSwNP compared to uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue as detected by the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full length TSLP was reduced up to 85%. NP extracts significantly enhanced IL-1β-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NP contain biologically relevant levels of TSLP activity. TSLP and its metabolic products may play an important role in the inflammation in CRSwNP.
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