IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma

Sci Rep. 2016 Nov 7:6:36551. doi: 10.1038/srep36551.

Abstract

Inflammation and angiogenesis are two hallmarks of carcinoma. The proinflammatory cytokine interleukin-17 (IL-17) facilitates angiogenesis in lung cancer; however, the underlying mechanism is not fully understood. In this study, tumour microvessel density (MVD) was positively associated with IL-17, interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial cell growth factor (VEGF) expression in human lung adenocarcinoma tissues, and it was increased in tumour tissues of A549-IL-17 cell-bearing nude mice. Importantly, positive correlations were also detected between IL-17 expression and IL-6, IL-8 and VEGF expression in human lung adenocarcinoma tissues. Furthermore, IL-6, IL-8 and VEGF production, as well as STAT1 phosphorylation, were increased in tumour tissues of A549-IL-17 cell-bearing nude mice in vivo and in A549 and H292 cells following IL-17 stimulation in vitro. In addition, STAT1 knockdown using an inhibitor and siRNA attenuated the IL-17-mediated increases in IL-6, IL-8 and VEGF expression in A549 and H292 cells. In conclusion, IL-17 may promote the production of the angiogenic inducers IL-6, IL-8 and VEGF via STAT1 signalling in lung adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma of Lung
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Cell Line, Tumor
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-6 / metabolism*
  • Interleukin-8 / metabolism*
  • Lung Neoplasms / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / metabolism
  • STAT1 Transcription Factor / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inducing Agents
  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-17
  • Interleukin-6
  • Interleukin-8
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A