title: 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.
abstract: 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.
authors.affiliation: Emergency Department, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xing
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Dongna
authors.initials: D
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D001665:Binding Sites; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D051218:Lymphocyte Antigen 96 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D044946:Biflavonoids; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D044945:Proanthocyanidins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C479579:procyanidin B1; D002392:Catechin; D048051:p38 Mitogen-Activated Protein Kinases