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

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)-alpha-induced inflammatory response in ECs. Our results show that stable overexpression of CCDC3 decreases, while stable knockdown of the endogenous CCDC3 increases TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1) at the mRNA and protein level in ECs. The I kappa B kinase inhibitor Bay 11-7082 completely blocks TNF-alpha-induced expression of VCAM-1, confirming that TNF-alpha-induced expression of VCAM-1 in ECs is nuclear factor kappa B (NF-kappa B) dependent. Stable overexpression of CCDC3 decreases TNF-alpha-induced p65 and p50 nuclear translocation and NF-kappa B transcriptional activity, suggesting that CCDC3 inhibits TNF-alpha-induced NF-kappa B activation in ECs. Similar to CCDC3 overexpression, both CCDC3-containing conditioned medium (CM) and purified CCDC3 decrease TNF-a-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-alpha/NF-kappa B-induced pro-inflammatory response in ECs, providing an insight into the functional role of CCDC3. (C) 2014 Elsevier Inc All rights reserved.