Extracellular IL-33 cytokine, but not endogenous nuclear IL-33, regulates protein expression in endothelial cells

Sci Rep. 2016 Oct 3;6:34255. doi: 10.1038/srep34255.


IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in health and disease. Extracellular IL-33 activates a growing number of target cells, including group 2 innate lymphoid cells, mast cells and regulatory T cells, but it remains unclear whether intracellular nuclear IL-33 has additional functions in the nucleus. Here, we used a global proteomic approach based on high-resolution mass spectrometry to compare the extracellular and intracellular roles of IL-33 in primary human endothelial cells, a major source of IL-33 protein in human tissues. We found that exogenous extracellular IL-33 cytokine induced expression of a distinct set of proteins associated with inflammatory responses in endothelial cells. In contrast, knockdown of endogenous nuclear IL-33 expression using two independent RNA silencing strategies had no reproducible effect on the endothelial cell proteome. These results suggest that IL-33 acts as a cytokine but not as a nuclear factor regulating gene expression in endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism*
  • Endothelium, Vascular / metabolism*
  • Extracellular Space / metabolism*
  • Gene Knockdown Techniques
  • Gene Silencing
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism
  • Interleukin-33 / physiology*
  • RNA / genetics
  • Tandem Mass Spectrometry


  • IL33 protein, human
  • Inflammation Mediators
  • Interleukin-33
  • RNA