机构：[1]Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China[2]Department of Clinical Laboratory, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650031, Yunnan Province, China云南省第一人民医院[3]Department of Clinical Laboratory, The First People’s Hospital of Yunnan Province, Kunming 650031, Yunnan Province, China云南省第一人民医院[4]Medical Faculty of Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China[5]Department of Clinical Laboratory,The First Affiliated Hospital of Kunming Medical University,Kunming 650034,Yunnan Province,China昆明医科大学附属第一医院医技科室医学检验科[6]Department of Clinical Laboratory, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, Yunnan Province, China[7]Department of Neurology, The First People’s Hospital of Yunnan Province, Kunming 650031, Yunnan Province, China云南省第一人民医院
Blood-brain barrier (BBB) destruction is associated with a variety of neurological diseases. Brain microvascular endothelial cells (BMECs) are the key constituent of BBB. Both matrix metalloproteinases-2/9 (MMP-2/9) and toll-like receptor-2 (TLR2) are coexpressed in BMECs and have been shown to play important roles in BBB breakdown. It is unknown whether TLR2 can regulate MMP-2/9 in BMECs. In this study, Pam3CSK4 was used to activate TLR2, and the expression of MMP-2/9 and tight junctions (TJs) in BBB was measured by quantitative real-time PCR and western blotting. Phosphoproteins were determined by western blotting. The inhibitors of mitogen-activated protein kinases (MAPKs) and NF-B were used to identify the signaling pathways by which TLR2 regulates the expression of MMP-2/9 in BMECs. This study showed that Pam3CSK4 upregulated the mRNA and protein expression of MMP-9 and downregulated MMP-2 and TJ expression in BMECs simultaneously. Pam3CSK4 also induced the phosphorylation of MAPKs and NF-B signaling pathways in BMECs. MMP-9 expression was found to decrease by pretreatment with inhibitors of ERK1/2 and JNK but not p38. However, the mRNA and protein expression of MMP-2 and MMP-9 increased after addition of a NF-B inhibitor. Our results indicated that Pam3CSK4 was able to upregulate MMP-9 expression through ERK1/2 and JNK signaling pathways, but the NF-B signaling pathway negatively regulated the effect of TLR2 on MMP-2 and MMP-9 expression in BMECs. The finding provides novel insight into the molecular mechanism of MMP-2/9 expression in BMECs.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81460188]; Applied Basic Research Project in Yunnan Province of China [2011FB148]; Applied Basic Combined Special Project of the Department of Science and Technology of Yunnan Province and Kunming Medical University [2013FB201]; Young and Middle-Aged Academic and Technological Leaders and Reserved Talents of Yunnan Province of China [2012HB028]; Health System Leaders of Yunnan Province of China [D-201235]; Academician WangLong-de Workstation
第一作者机构：[1]Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China[2]Department of Clinical Laboratory, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650031, Yunnan Province, China[3]Department of Clinical Laboratory, The First People’s Hospital of Yunnan Province, Kunming 650031, Yunnan Province, China[4]Medical Faculty of Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China
