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

• Published in: Molecular and cellular biochemistry Vol. 407; no. 1-2; pp. 89 - 95
• Main Authors: Xing, Jing, Li, Rui, Li, Nan, Zhang, Jian, Li, Yueqing, Gong, Ping, Gao, Dongna, Liu, Hui, Zhang, Yu
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2015
• Subjects: Anti-Inflammatory Agents - pharmacology; Biflavonoids - pharmacology; Binding Sites; Biochemistry; Biomedical and Life Sciences; Cardiology; Catechin - pharmacology; Cell Line; Gene Expression Regulation - drug effects; Humans; Life Sciences; Lipopolysaccharides - adverse effects; Lymphocyte Antigen 96 - chemistry; Lymphocyte Antigen 96 - genetics; Lymphocyte Antigen 96 - metabolism; Medical Biochemistry; Models, Molecular; Molecular Docking Simulation; Monocytes - cytology; Monocytes - drug effects; NF-kappa B - genetics; NF-kappa B - metabolism; Oncology; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Proanthocyanidins - pharmacology; Signal Transduction - drug effects; Toll-Like Receptor 4 - chemistry; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; THP1 cells; TLR4–MD-2 heterodimer; Anti-inflammatory; Procyanidin B1; LPS
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-015-2457-4

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.