Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKC? and PKC?1 inhibition.

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Abstract

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 ?mol/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 ?mol/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)-?B and protein kinase C (PKC)? and PKC?1 activation.CONCLUSION: HT, at nutritionally relevant concentrations, reduces MMP-9 and COX-2 induction in activated human monocytes via PKC? and PKC?1 inhibition, thus featuring novel anti-inflammatory properties. Overall, such results contribute to explaining the vascular protective effects by olive oil polyphenols in Mediterranean diets.

Autore Pugliese

Tutti gli autori

  • Scoditti E.; Nestola A.; Massaro M.A.; Calabriso N.; Storelli C.; De Caterina R.; Carluccio M.A.

Titolo volume/Rivista

Atherosclerosis

Anno di pubblicazione

2014

ISSN

0021-9150

ISBN

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