title: Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models.
abstract: High mobility group box 1 (HMGB1) mediates proinflammatory responses in inflammatory diseases. Lycopene found in tomatoes and tomato products has anti-oxidant, anti-cancer and antiinflammatory effects. The potential anti-inflammatory roles of lycopene in HMGB1-mediated proinflammatory responses in both primary human umbilical vein endothelial cells (HUVECs) and animal were investigated. The anti-inflammatory effects of lycopene were determined including permeability, monocyte adhesion and migration, and activation of proinflammatory proteins and HMGB1 receptors on HMGB1 activated HUVECs. In the in vivo model, the anti-inflammatory effect of lycopene was assessed by monitoring vascular permeability and migration of leukocytes to the peritoneal cavity of mice injected with lycopene. Lycopene inhibited lipopolysaccharide (LPS)-mediated release of HMGB1, expression of HMGB1-mediated tumor necrosis factor (TNF)-secretory phospholipase A2 (sPLA2)-IIA, and HMGB1-mediated pro-inflammatory signaling responses in endothelial cells. It did this through down-regulation of cell surface expression of cell adhesion molecules (CAMs), HMGB1 receptors, toll-like receptor (TLR)-2, and -4, and receptors for advanced glycation end products (RAGE). These findings suggest that lycopene promotes barrier integrity, inhibits monocyte adhesion and migration to HMGB1 activating HUVECs by blocking activation of proinflammatory cytokines and expression of CAMs and HMGB1 receptors, thereby showing its usefulness as a therapy for vascular inflammatory diseases.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Jae Woan
authors.initials: JW
authors.lastname: Bae
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D054505:Group V Phospholipases A2 / Q000096:biosynthesis; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D007249:Inflammation / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D000077276:Lycopene; D051379:Mice; D008813:Mice, Inbred ICR; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface / Q000187:drug effects; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002338:Carotenoids; D054505:Group V Phospholipases A2; D000077276:Lycopene