title: MDP up-regulates the gene expression of type I interferons in human aortic endothelial cells.
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.
authors.affiliation: Department of Geriatric Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China. cathay057@sina.com
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Lv
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
authors.forename: Lina
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Xiao
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Chen
authors.forename: Meifang
authors.initials: M
authors.lastname: Chen
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xie
authors.forename: Jinyue
authors.initials: J
authors.lastname: Hu
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine