Interleukin-17 Induces CC Chemokine Receptor 6 Expression and Cell Migration in Colorectal Cancer Cells
Interleukin-17 Induces CC Chemokine Receptor 6 Expression and Cell Migration in Colorectal Cancer Cells
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DOI：
10.1002/jcp.24796
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发表时间：
2015-07-01
影响因子：
5.6
通讯作者：
Huang, Wen-Shih
中科院分区：
文献类型：
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作者：
Chin, Chih-Chien;Chen, Cheng-Nan;Huang, Wen-Shih
CC趋化因子受体6(CCR6)及其配体CCL20参与了结直肠癌的发生和发展。此外，由名为Th17的T细胞亚群产生的白介素17(IL-17)已被确认为炎症反应中的重要参与者，并已成为炎症相关癌症的介质。然而，IL-17在结直肠癌发生发展中的作用仍有待探讨。本研究旨在探讨IL-17对结直肠癌细胞迁移的影响。以人结直肠癌HCT-116细胞为研究对象，研究IL-17对结直肠癌细胞CCR6表达和细胞迁移的影响。IL-17诱导HCT-116细胞跨Boyden小室膜迁移，并上调CCR6的表达水平。小干扰RNA(SiRNA)和中和抗体抑制CCR6可抑制IL-17诱导的细胞迁移。通过使用特定的抑制剂和短发夹状RNA(ShRNA)，我们证明ERK和p38通路的激活在IL-17诱导的CCR6表达和细胞迁移中起关键作用。启动子活性和转录因子的ELISA法检测表明，IL-17增强了HCT-116细胞的核因子-B-DNA结合活性。用特定的抑制剂和siRNA抑制NF-B的激活可阻断IL-17诱导的CCR6的表达。我们的发现支持这一假说，即IL-17刺激的CCR6上调可能在结直肠癌细胞迁移中发挥积极作用。J.细胞。物理。2015年，230：1430-1437。(C)2014年威利期刊公司，A Wiley Company
The CC chemokine receptor 6 (CCR6) and its ligand CCL20 are involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. In addition, interleukin-17 (IL-17), produced by a T cell subset named Th17, has been identified as an important player in inflammatory responses, and has emerged as a mediator in inflammation-associated cancer. However, the relevance of IL-17 in the development and progression of CRC still remains to be explored. This study aimed to investigate the effect of IL-17 on the cell migration of CRC cells. Human CRC HCT-116 cells were used to study the effect of IL-17 on CCR6 expression and cell migration in CRC cells. IL-17 treatment induced migration of HCT-116 cells across the Boyden chamber membrane and increased the expression level of the CCR6. Inhibition of CCR6 by small interfering RNA (siRNA) and neutralizing antibody inhibited IL-17-induced cell migration. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK and p38 pathways are critical for IL-17-induced CCR6 expression and cell migration. Promoter activity and transcription factor ELISA assays showed that IL-17 increased NF-B-DNA binding activity in HCT-116 cells. Inhibition of NF-B activation by specific inhibitors and siRNA blocked the IL-17-induced CCR6 expression. Our findings support the hypothesis that CCR6 up-regulation stimulated by IL-17 may play an active role in CRC cell migration. J. Cell. Physiol. 230: 1430-1437, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company