Abstract |
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-κB- DNA binding activity in HCT-116 cells. Inhibition of NF-κB 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.
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Authors | Chih-Chien Chin, Cheng-Nan Chen, Hsing-Chun Kuo, Chung-Sheng Shi, Meng Chiao Hsieh, Yi-Hung Kuo, Shui-Yi Tung, Kam-Fai Lee, Wen-Shih Huang |
Journal | Journal of cellular physiology
(J Cell Physiol)
Vol. 230
Issue 7
Pg. 1430-7
(Jul 2015)
ISSN: 1097-4652 [Electronic] United States |
PMID | 25201147
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 Wiley Periodicals, Inc. |
Chemical References |
- CCR6 protein, human
- Interleukin-17
- NF-kappa B
- Receptors, CCR6
- Extracellular Signal-Regulated MAP Kinases
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Cell Movement
(drug effects)
- Chemotaxis
(drug effects)
- Colorectal Neoplasms
- Extracellular Signal-Regulated MAP Kinases
(genetics, metabolism)
- HCT116 Cells
- Humans
- Interleukin-17
(pharmacology)
- NF-kappa B
(genetics, metabolism)
- Receptors, CCR6
(genetics, metabolism)
- Signal Transduction
- p38 Mitogen-Activated Protein Kinases
(genetics, metabolism)
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