MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells

Molecules

Qingshan Lv²  Mei Yang²  Xueting Liu¹  Lina Zhou¹  Zhilin Xiao²  Xiaobin Chen²  Meifang Chen²  Xiumei Xie² 

[1]Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China

[2]Department of Geriatric Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China

关键词: MDP;    NOD2;    interferon;    endothelial cells;    cytokine;   

DOI  :  10.3390/molecules17043599

来源: mdpi

【 摘 要 】

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 TNFα signaling, as HAECs did not express TNFα with the stimulation of MDP, and TNFα 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-1β, 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.