TSLP，IL-33及其受体在嗜酸粒细胞性伴有鼻息肉的慢性鼻—鼻窦炎上皮细胞中的相互作用
发布时间：2018-08-29 16:04
【摘要】：目的：尽管TSLP, IL-25和IL-33在Th2反应的启动和发展中发挥了作用,但它们在嗜酸粒细胞性及非嗜酸粒细胞性伴鼻息肉的慢性鼻-鼻窦炎Th反应的形成中所起的作用仍然不明。此研究旨在进一步探索TSLP,IL-25,IL-33和它们的受体在伴鼻息肉的慢性鼻-鼻窦炎中的表达关联,以及它们在人鼻粘膜上皮细胞中的相互调控机制。 方法：我们运用了免疫组织化学,实时定量PCR,酶联免疫吸附试验,Bio-Plex悬液芯片和流式细胞检测技术检测TSLP/TSLP受体(TSLPR)/IL-7受体α(IL-7Ra), IL-25/IL-17B受体(IL-17RB),和IL-33/膜型ST2(ST2L)/可溶型ST2(sST2)在鼻窦粘膜以及人鼻粘膜上皮细胞中的表达；应用人原代鼻粘膜上皮细胞气液交换面培养探究细胞因子及其受体在上皮细胞中的表达调控。 结果：嗜酸粒细胞性伴鼻息肉的慢性鼻-鼻窦炎相对于对照组和非嗜酸性伴鼻息肉的慢性鼻-鼻窦炎,TSLP/TSLPR/lL-7Ra和ST2L/sST2的信使RNA水平和蛋白质水平的表达在上皮细胞和间质均显著增高,尤其在上皮细胞中最明显。但IL-25/IL-17RB和IL-33在嗜酸粒细胞性伴鼻息肉的慢性鼻-鼻窦炎中并不增高。TSLP, TSLPR和ST2L的表达水平与嗜酸粒细胞性伴鼻息肉的慢性鼻-鼻窦炎的VAS评分、CT评分和所有组鼻窦粘膜中Th2细胞因子的表达呈正相关。ST2L的表达与TSLP及其受体的表达呈显著正相关。在人原代鼻粘膜上皮细胞培养中,TSLP可以诱导ST2L的表达,IL-33可以通过上调的ST2L再进一步促进TSLP的表达增加。另外,TSLP/TSLPR/IL-7Ra和ST2L可以由Th2型细胞因子诱导产生,然而,IL-25/IL-17RB和IL-33的表达可以被Th1/Th17型细胞因子分别上调。 结论：在嗜酸粒细胞性伴鼻息肉的慢性鼻-鼻窦炎中,TSLP, IL-33及它们的受体形成的正反馈环和Th2细胞因子都可以促进Th2炎症反应的发生发展。 目的：呼吸道病毒被认为是急性鼻-鼻窦炎的一个启动因素,但是其在慢性鼻-鼻窦炎(CRS)中的作用尚不清楚。本研究的目的是探讨常见的呼吸道病毒在CRS持续阶段中发挥的潜在作用。 方法：53位对照组受试者,61位不伴有鼻息肉的慢性鼻-鼻窦炎(CRSsNP)患者以及67位伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)患者被纳入研究。刮取中鼻道上皮细胞以定量PCR检测9种常见呼吸道病毒在各组中的数量。病人分为病毒阳性组和病毒阴性组比较临床症状数据。 结果：本实验检测了鼻病毒,流感病毒A、B亚型,副流感病毒1、2、3型,呼吸道合孢病毒和冠状病毒OC43、229E这9种常见呼吸道病毒。在对照组,CRSwNP及CRSsNP组中呼吸道病毒总体阳性率分别为75.47%,68.66%和73.77%,且无统计学差异,三组之间单种病毒数量及多种病毒数量均无统计学差异。VAS评分,CT评分,鼻内镜评分在病毒阳性组和病毒阴性组均无统计学差异。 结论：虽然常见的呼吸道病毒在病人中鼻道有较高的数量,但是CRSwNP及CRSsNP的持续阶段相较于对照组病毒数量都没有增加,常见的呼吸道病毒在CRS慢性炎症持续过程中的具体作用机理还需要进一步深入的研究。
[Abstract]:OBJECTIVE: Although TSLP, IL-25 and IL-33 play important roles in the initiation and development of Th2 response, their roles in the formation of Th response in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps are still unknown. The correlation between the expression and the mechanism of regulation in the epithelial cells of human nasal mucosa.
METHODS: Immunohistochemistry, real-time quantitative PCR, enzyme-linked immunosorbent assay, Bio-Plex suspension chip and flow cytometry were used to detect TSLP/TSLPR/IL-7 receptor alpha (IL-7Ra), IL-25/IL-17B receptor (IL-17RB), and IL-33/membrane ST2 (ST2L)/soluble ST2 (sST2) in nasal sinus mucosa and human nasal epithelial cells. The expression of cytokines and their receptors in human nasal epithelial cells was studied by gas-liquid exchange surface culture.
Results: Compared with control group and non-eosinophilic chronic rhinosinusitis with nasal polyps, the expression of TSLP/TSLPR/lL-7Ra and STL/sST2 messenger RNA and protein in epithelial and mesenchymal cells were significantly increased, especially in epithelial cells. The expression of TSLP, TSLPR and ST2L was positively correlated with VAS score, CT score and Th2 cytokine expression in nasal sinus mucosa of eosinophilic sinusitis with nasal polyps. In addition, TSLP/TSLPR/IL-7Ra and SSTL can be induced by Th2 cytokines. However, the expressions of IL-25/IL-17RB and IL-33 can be up-regulated by Th1/Th17 cytokines, respectively. Adjust.
Conclusion: TSLP, IL-33 and their receptors form positive feedback loops and Th2 cytokines can promote the development of Th2 inflammation in eosinophilic chronic rhinosinusitis with nasal polyps.
OBJECTIVE: Respiratory tract viruses are considered to be a trigger for acute rhinosinusitis, but their role in chronic rhinosinusitis (CRS) remains unclear.
METHODS: Fifty-three control subjects, 61 patients with chronic rhinosinusitis (CRSsNP) without nasal polyps and 67 patients with chronic rhinosinusitis (CRSwNP) with nasal polyps were enrolled in the study. The negative group was compared with clinical symptom data.
Results: The total positive rates of respiratory tract viruses were 75.47%, 68.66% and 73.77% in the control group, CRSwNP and CRSsNP, respectively, and there was no statistical difference among the three groups. There was no significant difference in the number of viruses and the number of viruses. There was no significant difference in VAS score, CT score and nasal endoscopy score between the virus positive group and the virus negative group.
CONCLUSION: Although the number of common respiratory viruses in the middle nasal meatus is higher, the number of CRSwNP and CRSsNP in the persistent stage of CRS is not increased compared with that in the control group. The specific mechanism of the common respiratory viruses in the process of chronic inflammation of CRS needs further study.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R765
[Abstract]:OBJECTIVE: Although TSLP, IL-25 and IL-33 play important roles in the initiation and development of Th2 response, their roles in the formation of Th response in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps are still unknown. The correlation between the expression and the mechanism of regulation in the epithelial cells of human nasal mucosa.
METHODS: Immunohistochemistry, real-time quantitative PCR, enzyme-linked immunosorbent assay, Bio-Plex suspension chip and flow cytometry were used to detect TSLP/TSLPR/IL-7 receptor alpha (IL-7Ra), IL-25/IL-17B receptor (IL-17RB), and IL-33/membrane ST2 (ST2L)/soluble ST2 (sST2) in nasal sinus mucosa and human nasal epithelial cells. The expression of cytokines and their receptors in human nasal epithelial cells was studied by gas-liquid exchange surface culture.
Results: Compared with control group and non-eosinophilic chronic rhinosinusitis with nasal polyps, the expression of TSLP/TSLPR/lL-7Ra and STL/sST2 messenger RNA and protein in epithelial and mesenchymal cells were significantly increased, especially in epithelial cells. The expression of TSLP, TSLPR and ST2L was positively correlated with VAS score, CT score and Th2 cytokine expression in nasal sinus mucosa of eosinophilic sinusitis with nasal polyps. In addition, TSLP/TSLPR/IL-7Ra and SSTL can be induced by Th2 cytokines. However, the expressions of IL-25/IL-17RB and IL-33 can be up-regulated by Th1/Th17 cytokines, respectively. Adjust.
Conclusion: TSLP, IL-33 and their receptors form positive feedback loops and Th2 cytokines can promote the development of Th2 inflammation in eosinophilic chronic rhinosinusitis with nasal polyps.
OBJECTIVE: Respiratory tract viruses are considered to be a trigger for acute rhinosinusitis, but their role in chronic rhinosinusitis (CRS) remains unclear.
METHODS: Fifty-three control subjects, 61 patients with chronic rhinosinusitis (CRSsNP) without nasal polyps and 67 patients with chronic rhinosinusitis (CRSwNP) with nasal polyps were enrolled in the study. The negative group was compared with clinical symptom data.
Results: The total positive rates of respiratory tract viruses were 75.47%, 68.66% and 73.77% in the control group, CRSwNP and CRSsNP, respectively, and there was no statistical difference among the three groups. There was no significant difference in the number of viruses and the number of viruses. There was no significant difference in VAS score, CT score and nasal endoscopy score between the virus positive group and the virus negative group.
CONCLUSION: Although the number of common respiratory viruses in the middle nasal meatus is higher, the number of CRSwNP and CRSsNP in the persistent stage of CRS is not increased compared with that in the control group. The specific mechanism of the common respiratory viruses in the process of chronic inflammation of CRS needs further study.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R765
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