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 TNFα (tumour necrosis factor α)-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 TNFα-induced expression of chemokines and adhesive molecules in HUVECs. Furthermore, forced expression of Zc3h12c decreased TNFα-induced IKKα/β [IκB (inhibitor of nuclear factor κB) kinase α/β], IκBα phosphorylation and p65 nuclear translocation, suggesting that Zc3h12c exerted its anti-inflammatory function probably by suppressing the NF-κB (nuclear factor κB) pathway. Thus Zc3h12c is an endogenous inhibitor of TNFα-induced inflammatory signalling in HUVECs and might be a therapeutic target in vascular inflammatory diseases.
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Research Article|
March 14 2013
Zc3h12c inhibits vascular inflammation by repressing NF-κB activation and pro-inflammatory gene expression in endothelial cells
Ling Liu;
Ling Liu
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
†Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, P.R. China
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Zhou Zhou;
Zhou Zhou
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
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Shengping Huang;
Shengping Huang
‡Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, U.S.A.
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Yanhong Guo;
Yanhong Guo
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
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Yanbo Fan;
Yanbo Fan
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
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Ji Zhang;
Ji Zhang
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
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Jifeng Zhang;
Jifeng Zhang
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
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Mingui Fu;
Mingui Fu
1
‡Department of Basic Medical Science, School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, U.S.A.
1Correspondence may be addressed to either of these authors (email fum@umkc.edu or echenum@med.umich.edu).
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Y. Eugene Chen
Y. Eugene Chen
1
*Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A.
1Correspondence may be addressed to either of these authors (email fum@umkc.edu or echenum@med.umich.edu).
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Publisher: Portland Press Ltd
Received:
January 04 2013
Revision Received:
January 25 2013
Accepted:
January 29 2013
Accepted Manuscript online:
January 29 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 451 (1): 55–60.
Article history
Received:
January 04 2013
Revision Received:
January 25 2013
Accepted:
January 29 2013
Accepted Manuscript online:
January 29 2013
Citation
Ling Liu, Zhou Zhou, Shengping Huang, Yanhong Guo, Yanbo Fan, Ji Zhang, Jifeng Zhang, Mingui Fu, Y. Eugene Chen; Zc3h12c inhibits vascular inflammation by repressing NF-κB activation and pro-inflammatory gene expression in endothelial cells. Biochem J 1 April 2013; 451 (1): 55–60. doi: https://doi.org/10.1042/BJ20130019
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