期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 407, 期 1-2, 页码 89-95出版社
SPRINGER
DOI: 10.1007/s11010-015-2457-4
关键词
Anti-inflammatory; LPS; Procyanidin B1; THP1 cells; TLR4-MD-2 heterodimer
类别
资金
- Young Starting Foundation of the First Affiliated Hospital, Dalian Medical University [QN2012008]
- Dalian Science and Technology Planning Project (guidance project)
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)-alpha 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)-kappa B 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-kappa B 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-alpha 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-kappa B protein, as well as mRNA levels of MD-2, TRAF-6, and NF-kappa B (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-kappa B signaling pathways.
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