Modulation of the MMP-9 expression by olive oil phenols

Although the beneficial effects of olive oil consumption on human health are well recognized, the functions and the mechanisms through which specific components of olive oil exert their effects still need to be fully deciphered. Although in vivo studies suggest that these compounds are responsible for the anti-inflammatory activity and anti-atherosclerotic actions of olive oil, less is known on the direct effects and mechanisms of action of these molecules in circulating cells. Monocytes participate in the early stages of atherosclerosis and, by expressing several molecules, including metalloproteases (MMPs), contribute to amplify the inflammatory response. With the aim of elucidating the mechanisms through which olive oil-derived phenols are beneficial on markers related to cardiovascular diseases, we investigated the effects of an olive oil phenolic extract (PE) and the main individual phenolic compounds (PCs, namely oleuropein aglycone, apigenin, luteolin, tyrosol and hydroxytyrosol) on the modulation of MMP-9 in monocytes. We found that PE significantly counteracts the effect of TNFalpha on the expression and secretion of MMP-9. Oleuropein aglycone resulted to be active at the concentrations found in PE although other compounds probably contribute to the activity exhibited by the extract. We demonstrated that PE acts at the transcriptional level preventing the stimulation of MMP-9 promoter activity. Finally we found that the effect of PE on gene expression is ascribable to impairment of NF-kappaB signalling. We assayed individual compounds present in PE that could contribute to the biological activity. Our findings regarding the ability of both flavonoids to down-regulate the MMP-9 promoter and to attenuate the NF-kappaB-driven transcription are much higher than those found in PE used in our experiments thus excluding a role of these compounds in the effects exerted by PE. In the present study we clearly demonstrate that PE inhibits MMP-9 expression thus supporting the hypothesis that inhibition of proteolytic activity by PCs could be, at least in part, responsible for the reduction of invasiveness of tumour cells. In this context our study elucidates some of the molecular mechanisms through which olive oil, a phenolic rich source, can be beneficial to human health, as widely demonstrated by in vivo studies.