caa a22 4500 606235744 CHVBK 20210128101244.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2457-4 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2457-4 Anti-inflammatory effect of procyanidin B1 on LPS-treated THP1 cells via interaction with the TLR4-MD-2 heterodimer and p38 MAPK and NF-κB signaling [Elektronische Daten] [Jing Xing, Rui Li, Nan Li, Jian Zhang, Yueqing Li, Ping Gong, Dongna Gao, Hui Liu, Yu Zhang] Anti-inflammatory effects of procyanidin B1 have been documented; however, the molecular mechanisms that are involved have not been fully elucidated. Molecular docking models were applied to evaluate the binding capacity of lipopolysaccharide (LPS) and procyanidin B1 with the toll-like receptor (TLR)4/myeloid differentiation factor (MD)-2 complex. LPS-induced production of the proinflammatory cytokine tumor necrosis factor (TNF)-α in a human monocyte cell line (THP1) was measured by ELISA. mRNA expression of MD-2, TLR4, TNF receptor-associated factor (TRAF)-6, and nuclear factor (NF)-κB was measured by real-time PCR with or without an 18-h co-treatment with procyanidin B1. In addition, protein expression of phosphorylated p38 mitogen-activated protein kinase (MAPK) and NF-κB was determined by Western blotting. Structural modeling studies identified Tyr296 in TLR4 and Ser120 in MD-2 as critical sites for hydrogen bonding with procyanidin B1, similar to the sites occupied by LPS. The production of TNF-α was significantly decreased by procyanidin B1 in LPS-treated THP1 cells (p<0.05). Procyanidin B1 also significantly suppressed levels of phosphorylated p38 MAPK and NF-κB protein, as well as mRNA levels of MD-2, TRAF-6, and NF-κB (all p<0.05). Procyanidin B1 can compete with LPS for binding to the TLR4-MD-2 heterodimer and suppress downstream activation of p38 MAPK and NF-κB signaling pathways. Springer Science+Business Media New York, 2015 Anti-inflammatory nationallicence LPS nationallicence Procyanidin B1 nationallicence THP1 cells nationallicence TLR4-MD-2 heterodimer nationallicence Xing Jing Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Li Rui Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Li Nan Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Zhang Jian Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Li Yueqing College of Pharmaceutical Science and Technology, Dalian University of Technology, 116024, Dalian, China aut Gong Ping Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Gao Dongna Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Liu Hui Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Zhang Yu Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 89-95 0300-8177 407:1-2<89 2015 407 11010 https://doi.org/10.1007/s11010-015-2457-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2457-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xing Jing Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Li Rui Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Li Nan Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Zhang Jian Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Li Yueqing College of Pharmaceutical Science and Technology, Dalian University of Technology, 116024, Dalian, China aut NATIONALLICENCE 700 1- Gong Ping Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Gao Dongna Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Liu Hui Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 700 1- Zhang Yu Emergency Department, First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 89-95 0300-8177 407:1-2<89 2015 407 11010