title: Rhein lysinate inhibits monocyte adhesion to human umbilical vein endothelial cells by blocking p38 signaling pathway.
abstract: The objective of this study was to investigate the effect of rhein lysinate (RHL) on monocyte adhesion and its mechanism. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the growth inhibition by drugs. The monocyte chemoattractant protein (MCP)-1 levels were assayed using MCP-1 ELISA. The expression of proteins was detected by Western blotting analysis. The results indicated that RHL inhibited monocyte adhesion in a dose- and time-dependent manner. RHL (<20 μmol/L) and lipopolysaccharide (LPS) had no effect on viability of human umbilical vein endothelial cells. Therefore, 20 μmol/L RHL was selected for this study. RHL inhibited secretion of MCP-1 induced by LPS and expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1. In the meantime, both RHL and p38 inhibitor (SB203580) inhibited phosphorylation of p38 and mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK-2) and transcription and expression of ICAM-1 and VCAM-1. In conclusion, RHL inhibits the transcription and expression of ICAM-1 and VCAM-1 by the p38/MAPKAPK-2 signaling pathway, and the effect of RHL on transcription and expression of ICAM-1 and VCAM-1 is similar to p38 inhibitor. RHL could be a prophylactic drug for atherosclerosis.
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Room 1010, No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing, 100730, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Lin
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Zhen
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.forename: Ping
authors.initials: P
authors.lastname: Tu
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000880:Anthraquinones; D018932:Chemokine CCL2; D007093:Imidazoles; D018799:Intercellular Adhesion Molecule-1; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008239:Lysine; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D019010:Vascular Cell Adhesion Molecule-1; D000099190:MAP-Kinase-Activated Kinase 2; C111835:CCL2 protein, human; C583741:rhein lysinate; C093642:SB 203580