Effects of flavonoids on the expression of the pro-inflammatory response in human monocytes induced by ligation of the receptor for AGEs

• Published in: Molecular nutrition & food research 2006-12, Vol.50 (12), p.1129-1139
• Main Authors: Huang, Shang-Ming, Wu, Chi-Hao, Yen, Gow-Chin
• Format: Article
• Language: English
• Subjects: AGEs; Antioxidants - pharmacology; Catechin; Catechin - pharmacology; CD18 Antigens - genetics; Cell Line; Chemokine CCL2 - genetics; Cyclooxygenase 2 - genetics; Cytokine; Cytokines - genetics; Flavonoids - pharmacology; Gene Expression - drug effects; Humans; Inflammation - metabolism; Interleukin-1beta - genetics; Mitogen-Activated Protein Kinases - metabolism; Monocytes - physiology; Oxidative stress; Oxidative Stress - drug effects; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Quercetin; Quercetin - pharmacology; Receptor for Advanced Glycation End Products; Receptors, Immunologic - drug effects; Receptors, Immunologic - physiology; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.200600075

Increasing evidence has shown advanced glycation end products (AGEs) receptor ligation (RAGE) to be an important part of complex interactions of the oxidative stress and pro‐inflammatory responses. In this study, flavonoids were used to monitor the protective effects against the oxidative damage and inflammation mediated by AGEs in human monocytes. S100B (RAGE ligand) treatment in human THP‐1 monocytic cells (THP‐1) significantly increased gene expression of the pro‐inflammatory cytokines TNF‐α and IL‐1β; chemokines MCP‐1 and IP‐10; adhesion factors platelet endothelial cell adhesion molecule (PECAM‐1) and β2‐integrin; and pro‐inflammatory cyclooxygenase‐2 (COX‐2). S100B treatment with quercetin and catechin in THP‐1 cells had inhibitory effects on the expression of pro‐inflammatory genes and protein levels. Quercetin and catechin could regulate S100B‐activated oxidant stress‐sensitive pathways through blocking p47phox protein expression. Treatment with quercetin and catechin could eliminate reactive oxygen species (ROS) to reduce oxidative stress stimulated by S100B in THP‐1 cells. Quercetin and catechin also showed different regulatory abilities on mitogen‐activated protein kinase (MAPK) signaling pathways by inhibiting protein expression in S100B‐stimulated inflammatory responses in THP‐1 cells. This study suggests that quercetin and catechin may be of benefit for diabetic vascular complications due to its antioxidant abilities against AGE‐mediated oxidative stress through oxidative stress‐sensitive and oxidative stress‐responsive signaling pathways, which lead to inflammation in human monocytes.