期刊
BIOCHEMICAL JOURNAL
卷 451, 期 -, 页码 55-60出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130019
关键词
human umbilical vein endothelial cell (HUVEC); inflammation; nuclear factor kappa B (NF-kappa B); vascular cell adhesion molecule-1 (VCAM-1); zinc finger CCCH-type-containing 12C (Zc3h12c)
资金
- National Institutes of Health [HL068878, HL089544, HL098794]
- American Heart Association [0840025N]
Endothelial activation characterized by the expression of multiple chemokines and adhesive molecules is a critical initial step of vascular inflammation, which results in recruitment of leucocytes into the sub-endothelial layer of the vascular wall and triggers vascular inflammatory diseases such as atherosclerosis. Although inhibiting endothelial inflammation has already been well recognized as a therapeutic strategy in vascular inflammatory diseases, the therapeutic targets are still elusive. In the present study we found that Zc3h12c (zinc finger CCCH-type-containing 12C), a recently discovered CCCH zinc finger-containing protein, significantly inhibited the endothelial cell inflammatory response in vitro. Overexpression of Zc3h12c significantly attenuated TNF alpha (tumour necrosis factor alpha)-induced expression of chemokines and adhesive molecules, and thus reduced monocyte adherence to HUVECs (human umbilical vein endothelial cells). Conversely, siRNA (small interfering RNA)-mediated knockdown of Zc3h12c increased the TNF alpha-induced expression of chemokines and adhesive molecules in HUVECs. Furthermore, forced expression of Zc3h12c decreased TNFa-induced IKK alpha/beta [I kappa B (inhibitor of nuclear factor kappa B) kinase alpha/beta], I kappa B alpha phosphorylation and p65 nuclear translocation, suggesting that Zc3h12c exerted its anti-inflammatory function probably by suppressing the NF-kappa B (nuclear factor kappa B) pathway. Thus Zc3h12c is an endogenous inhibitor of TNF alpha-induced inflammatory signalling in HUVECs and might be a therapeutic target in vascular inflammatory diseases.
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