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Interleukin-17 induces CC chemokine receptor 6 expression and cell migration in colorectal cancer cells.

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.
AuthorsChih-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
JournalJournal of cellular physiology (J Cell Physiol) Vol. 230 Issue 7 Pg. 1430-7 (Jul 2015) ISSN: 1097-4652 [Electronic] United States
PMID25201147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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