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MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells
Department of Geriatric Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China
Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China
* Author to whom correspondence should be addressed.
Received: 19 February 2012; in revised form: 16 March 2012 / Accepted: 20 March 2012 / Published: 23 March 2012
Abstract: Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs) with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF) 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.
Keywords: MDP; NOD2; interferon; endothelial cells; cytokine
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Lv, Q.; Yang, M.; Liu, X.; Zhou, L.; Xiao, Z.; Chen, X.; Chen, M.; Xie, X.; Hu, J. MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells. Molecules 2012, 17, 3599-3608.
Lv Q, Yang M, Liu X, Zhou L, Xiao Z, Chen X, Chen M, Xie X, Hu J. MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells. Molecules. 2012; 17(4):3599-3608.
Lv, Qingshan; Yang, Mei; Liu, Xueting; Zhou, Lina; Xiao, Zhilin; Chen, Xiaobin; Chen, Meifang; Xie, Xiumei; Hu, Jinyue. 2012. "MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells." Molecules 17, no. 4: 3599-3608.