Cui Guanglin, Yang Hang, Zhao Jianbo, Yuan Aping, Florholmen Jon
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China,
Pathol Oncol Res. 2015 Jan;21(1):139-46. doi: 10.1007/s12253-014-9799-1. Epub 2014 May 25.
Considerable evidence has suggested that chronic inflammation is a causative factor in the development of human colorectal cancer (CRC). Interleukin (IL)-17A produced mainly by Th17 cells is a novel proinflammatory cytokine and increased IL-17A is associated with colorectal neoplastic transformation. In this study, we have evaluated the expression of IL-17A in the adjacent tissues along the colorectal adenoma-carcinoma sequence. The expression of IL-17A in the adjacent tissues of colorectal adenoma (adenoma-adjacent, n = 32) and sporadic CRC (CRC-adjacent, n = 45) was examined. In addition, the expression pattern of Th17 cell differentiation stimulators (IL-1β, IL-6 and IL-23A) in the adjacent tissues were also examined. The results showed that the expression level of IL-17A mRNA was non-statistically increased (4-fold higher) in the adenoma-adjacent tissues and it became significantly increased (9-fold higher) in the CRC-adjacent tissues as compared with the control. The expression level of IL-17A in the CRC-adjacent tissues was not associated with CRC clinicopathological parameters and overall survival. Immunohistochemistry confirmed an increased density of intraepithelial IL-17A expressing cells in the CRC-adjacent tissues. The Th17 cell differentiation simulators IL-1β and IL-6 were also shown in an increase trend from the adenoma-adjacent to CRC-adjacent tissues. These results provide evidence that IL-17A/Th17 response is enhanced in the adjacent tissues during the colorectal neoplastic transformation.
大量证据表明，慢性炎症是人类结直肠癌（CRC）发生发展的一个致病因素。主要由Th17细胞产生的白细胞介素（IL）-17A是一种新型促炎细胞因子，IL-17A水平升高与结直肠肿瘤转化相关。在本研究中，我们评估了IL-17A在结直肠腺瘤-癌序列相邻组织中的表达。检测了结直肠腺瘤相邻组织（腺瘤相邻，n = 32）和散发性CRC相邻组织（CRC相邻，n = 45）中IL-17A的表达。此外，还检测了相邻组织中Th17细胞分化刺激因子（IL-1β、IL-6和IL-23A）的表达模式。结果显示，与对照组相比，腺瘤相邻组织中IL-17A mRNA表达水平无统计学意义的升高（高4倍），而在CRC相邻组织中显著升高（高9倍）。CRC相邻组织中IL-17A的表达水平与CRC临床病理参数及总生存期无关。免疫组织化学证实CRC相邻组织中上皮内IL-17A表达细胞密度增加。Th17细胞分化刺激因子IL-1β和IL-6也呈现出从腺瘤相邻组织到CRC相邻组织的升高趋势。这些结果提供了证据，表明在结直肠肿瘤转化过程中，相邻组织中的IL-17A/Th17反应增强。
