title: Protection against chemotaxis in the anti-inflammatory effect of bioactives from tomato ketchup.
abstract: The consumption of tomato products has been associated with a decreased risk for chronic inflammatory diseases. In this study, the anti-inflammatory potential of tomato ketchup was evaluated by studying the effect of tomato ketchup extracts and bioactives from tomato ketchup on human monocytes and vascular endothelial cells (HUVEC). HUVEC were pre-treated for 1 h with either individual bioactives (7.5 µM lycopene, 1.4 µM α-tocopherol or 55 µM ascorbic acid) or a combination of these three compounds, or with the hydrophilic or lipophilic tomato ketchup extracts or with the two extracts combined. After the pretreatment, the cells were washed and challenged with TNF-α (10 ng/ml) for 6 h. The medium was used for the determination of the release of cytokines and the chemotaxis of monocytes. Inflammatory protein expression and production were assayed with real-time RT-PCR and ELISA. It was found that tomato ketchup extracts significantly reduced gene expression and release of the pro-inflammatory cytokines TNF-α and IL-8 in HUVEC after the inflammatory challenge, whereas the release of the anti-inflammatory cytokine IL-10 was increased. Chemotaxis was effectively impeded as demonstrated by a reduced monocyte migration. This effect correlated with the reduction of IL-8 production in the presence of the test compounds and extracts. The results consistently emphasize the contribution of lycopene to the anti-inflammatory effect of tomato ketchup. Other compounds in tomato ketchup such as α-tocopherol and ascorbic acid appeared to strengthen the anti-inflammatory effect of lycopene. The tomato ketchup extracts subtly interfered with several inflammatory phases that inhibit chemotaxis. Such a pleotropic mode of action exemplifies its potential mitigation of diseases characterized by prolonged low grade inflammation.
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Merel
authors.initials: M
authors.lastname: Hazewindus
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Antje R
authors.initials: AR
authors.lastname: Weseler
authors.affiliation: Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D005511:Food Handling; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018551:Solanum lycopersicum / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010936:Plant Extracts; D024502:alpha-Tocopherol; D001205:Ascorbic Acid