1. Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKCα and PKCβ1 inhibition.
- Author
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Scoditti E, Nestola A, Massaro M, Calabriso N, Storelli C, De Caterina R, and Carluccio MA
- Subjects
- Diet, Mediterranean, Down-Regulation, Enzyme Activation, Humans, Inflammation, Leukocytes, Mononuclear drug effects, Macrophages metabolism, Monocytes cytology, NF-kappa B p50 Subunit metabolism, Olive Oil, Oxidation-Reduction, Oxidative Stress, Phenylethyl Alcohol chemistry, Phorbol Esters, Plant Oils chemistry, Polyphenols chemistry, Signal Transduction, U937 Cells, Cyclooxygenase 2 metabolism, Gene Expression Regulation, Enzymologic drug effects, Matrix Metalloproteinase 9 metabolism, Monocytes enzymology, Phenylethyl Alcohol analogs & derivatives, Protein Kinase C beta metabolism, Protein Kinase C-alpha metabolism
- Abstract
Objective: Hydroxytyrosol (HT), the major olive oil antioxidant polyphenol in cardioprotective Mediterranean diets, is endowed with anti-inflammatory and anti-atherosclerotic activity. The production of cyclooxygenase (COX)-2-dependent inflammatory eicosanoids and the functionally linked release of matrix metalloproteinase (MMP)-9 by macrophages likely contribute to plaque instability leading to acute coronary events. Objective of the study was to examine the HT effects on inflammatory markers in human activated monocytes, including MMP-9 and COX-2 activity and expression and explore HT underlying mechanisms., Methods and Results: Human peripheral blood mononuclear cells (PBMC) and U937 monocytes were treated with 1-10 μmol/L HT before activation with phorbol myristate acetate (PMA). HT blunted monocyte matrix invasive potential and reduced MMP-9 release and expression at zymography, ELISA and RT-PCR, with an IC50 = 10 μmol/L ( P< 0.05), without affecting tissue inhibitor of metalloproteinase (TIMP)-1. Moreover, HT inhibited prostaglandin (PG)E2 production and COX-2 expression, without affecting COX-1. These effects were mediated by inhibition of transcription factor nuclear factor (NF)-κB and protein kinase C (PKC)α and PKCβ1 activation., Conclusion: HT, at nutritionally relevant concentrations, reduces MMP-9 and COX-2 induction in activated human monocytes via PKCα and PKCβ1 inhibition, thus featuring novel anti-inflammatory properties. Overall, such results contribute to explaining the vascular protective effects by olive oil polyphenols in Mediterranean diets., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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