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Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKCα and PKCβ1

Egeria Scoditti1, Alessia Nestola1, Marika Massaro1

  • 1National Research Council (CNR), Institute of Clinical Physiology (IFC), Lecce, Italy.

Atherosclerosis
|January 10, 2014
PubMed
Abstract

Insights

Hydroxytyrosol (HT), an olive oil polyphenol, reduces inflammatory markers like MMP-9 and COX-2 in human monocytes. These findings highlight HT's anti-inflammatory properties and potential vascular protection in Mediterranean diets.

Area of Science:

  • Cardiovascular Research
  • Nutritional Science
  • Immunology

Background:

  • Hydroxytyrosol (HT) is a key olive oil polyphenol with known anti-inflammatory and anti-atherosclerotic effects.
  • Macrophage-derived cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 contribute to plaque instability and acute coronary events.

Purpose of the Study:

  • To investigate the effects of HT on inflammatory markers in human activated monocytes.
  • To examine HT's impact on MMP-9 and COX-2 expression and activity.
  • To elucidate the underlying mechanisms of HT's action.

Main Methods:

  • Human peripheral blood mononuclear cells (PBMC) and U937 monocytes were treated with HT (1-10 μmol/L) prior to activation.
  • Assays included zymography, ELISA, and RT-PCR to measure MMP-9 and COX-2.
  • Involvement of nuclear factor (NF)-κB and protein kinase C (PKC) isoforms was assessed.

Main Results:

  • HT significantly reduced monocyte matrix invasion, MMP-9 release, and expression (IC50 = 10 μmol/L).
  • HT inhibited prostaglandin (PG)E2 production and COX-2 expression without affecting COX-1.
  • These effects were linked to the inhibition of NF-κB and PKCα/β1 activation.

Conclusions:

  • HT demonstrates novel anti-inflammatory properties by reducing MMP-9 and COX-2 induction in activated human monocytes.
  • The mechanism involves inhibition of PKCα and PKCβ1 signaling pathways.
  • These findings support the vascular protective role of olive oil polyphenols in Mediterranean diets.
Keywords:
Cyclooxygenase-2HydroxytyrosolInflammationMatrix metalloproteinase-9Nuclear factor-κBOxidative stressProtein kinase C

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