Coiled-coil domain containing 3 (CCDC3) represses tumor necrosis factor-α/nuclear factor κB-induced endothelial inflammation

Cell Signal. 2014 Dec;26(12):2793-800. doi: 10.1016/j.cellsig.2014.08.025. Epub 2014 Sep 2.


Coiled-coil domain containing 3 (CCDC3) is a newly identified secretory protein that is expressed in vascular endothelial cells (ECs) and adipose tissues. Here, we investigate the role of CCDC3 in tumor necrosis factor (TNF)-α-induced inflammatory response in ECs. Our results show that stable overexpression of CCDC3 decreases, while stable knockdown of the endogenous CCDC3 increases TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) at the mRNA and protein level in ECs. The IκB kinase inhibitor Bay 11-7082 completely blocks TNF-α-induced expression of VCAM-1, confirming that TNF-α-induced expression of VCAM-1 in ECs is nuclear factor κB (NF-κB) dependent. Stable overexpression of CCDC3 decreases TNF-α-induced p65 and p50 nuclear translocation and NF-κB transcriptional activity, suggesting that CCDC3 inhibits TNF-α-induced NF-κB activation in ECs. Similar to CCDC3 overexpression, both CCDC3-containing conditioned medium (CM) and purified CCDC3 decrease TNF-α-induced expression of VCAM-1 in receiving ECs, suggesting a paracrine/autocrine function of CCDC3. Interestingly, CCDC3 in CM can enter the receiving ECs. Taken together, our work demonstrates that CCDC3 represses TNF-α/NF-κB-induced pro-inflammatory response in ECs, providing an insight into the functional role of CCDC3.

Keywords: Coiled-coil domain containing 3 (CCDC3); Endothelial inflammation; Nuclear factor κB (NF-κB); Tumor necrosis factor α (TNF-α); Vascular cell adhesion molecule-1 (VCAM-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autocrine Communication / drug effects
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology*
  • NF-kappa B / metabolism*
  • Paracrine Communication / drug effects
  • Proteins / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • CCDC3 protein, human
  • Culture Media, Conditioned
  • NF-kappa B
  • Proteins
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1