Intrinsic expression of Th2 cytokines in urothelium of congenital ureteropelvic junction obstruction
Intrinsic expression of Th2 cytokines in urothelium of congenital ureteropelvic junction obstruction
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DOI：
10.1111/j.1523-1755.2005.67120.x
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发表时间：
2005-02-01
影响因子：
19.6
通讯作者：
Tang, MJ
中科院分区：
文献类型：
--
作者：
Chiou, YY;Shieh, CC;Tang, MJ
背景尿路上皮（尿液和下方结缔组织之间的尿路屏障）产生细胞因子的能力可能会加剧先天性肾盂输尿管连接部阻塞（UPJ-O）疾病的发病机制。尿路梗阻在人类尿路梗阻中的作用很少被描述。在这项研究中，我们调查的免疫病理学特征，细胞因子的生产，尿路上皮细胞在儿童先天性UPJ-O。24例接受肾盂成形术的先天性UPJ-O患儿入选。观察UPJ-O节段的形态学改变、病理学改变及炎症反应。采用免疫组化（IHC）、原位杂交（ISH）和尿酶联免疫吸附试验（ELISA）检测尿中细胞因子和趋化因子的表达，并与对照组进行比较。UPJ-O患者中常出现伴有Ki 67过度表达的尿路上皮不典型或单纯增生。有不同程度的炎性细胞和嗜酸性粒细胞浸润。免疫组化和原位杂交检测到UPJ-0段的尿中IL-5和eotaxin的表达增强，组织肥大细胞的脱颗粒增强。IL-4、IFN-γ和TNF-α检测不到。从梗阻肾收集的尿液中检测到显著更高水平的尿IL-5、IFN-γ和嗜酸性粒细胞趋化因子。其中，尿IL 5和/或IFN-γ水平升高与梗阻性尿路病变的严重程度相关（P < 0.05）。尿路上皮与肠道和呼吸道上皮一样，在免疫调节中起着积极的作用，并可能导致先天性UPJ-O发病机制的恶化。许多嗜酸性粒细胞相关的疾病细胞因子，可导致肥大细胞的脱粒，是UPJ-O尿路上皮病的主要调节因子。
Background. The cytokine-producing ability of urothelium, a urinary tract barrier between urine and underlying connective tissue, may exacerbate the pathogenesis of congenital ureteropelvic junction obstruction (UPJ-O) disease. A role for urothelium in human urinary tract obstruction has rarely been described. In this study, we investigated the immunopathologic characteristics of, and cytokine production by, urothelium in children with congenital UPJ-O.Methods. Twenty-four children with congenital UPJ-O who had received pyeloplasty were enrolled. Morphologic abnormalities and pathologic and inflammatory changes of UPJ-O segments were studied. Expression of cytokines and chemokines in urothelium was investigated and compared with control tissue by immunohistochemistry (IHC), in situ hybridization (ISH), and urinary enzyme-linked immunosorbent assay (ELISA).Results. Atypical or simple hyperplasia of the urothelium with evidence of Ki67 over-expression was found frequently in UPJ-O. There were variable degrees of inflammatory cell and eosinophil infiltration. Augmented expression of IL-5 and eotaxin detected by IHC and ISH, and enhanced degranulation of tissue mast cells were observed in the urothelium of UPJ-O segments. IL-4, IFN-gamma, and TNF-alpha were undetectable. Significantly higher levels of urinary IL-5, IFN-gamma, and eotaxin were detected in urine collected from the obstructed kidney. Among these, high urinary IL5 and/or IFN-gamma levels were associated with more severe obstructive uropathy (P < 0.05).Conclusion. Urothelium, like intestinal and respiratory epithelia, plays an active role in immunoregulation and may contribute to exacerbation of the pathogenesis of congenital UPJ-O. Many eosinophil-associated disease cytokines, which can lead to the degranulation of mast cells, are predominant regulators in UPJ-O urothelium.