IMMUNOMODULATORY EFFECTS OF PHENOLIC COMPOUNDS FROM EXTRA-VIRGIN OLIVE OIL IN INTESTINAL EPITHELIAL CELLS

It is known that olive oil, one of the main components of Mediterranean diet, contain several phenolic compounds (i.e. oleuropein aglycone, luteolin, apigenin) with antioxidant activities; thus these compounds could possess a protective role in specific pathological conditions, such as the inflammatory diseases. Aim of the present work was to investigate the immunomodulatory effects of olive oil phenols (OPs) on intestinal epithelial cells (Caco-2). Based on current knowledge on intestinal inflammation, we focused on NF-kB signalling and expression and secretion of IL-8, a typical NF-kB regulating gene, which are rapidly induced in response to pro-inflammatory cytokines and is involved in the acute phase of gastrointestinal inflammation. The study was performed using a phenolic extract from virgin olive oil (OPs) characterized by mass spectrometry and Caco-2 cells were treated with different stimuli (IL-1β, TNFα or LPS) that activate NF-kB by different mechanisms. We found that TNFα and IL-1β induced NF-kB driven transcription and OPs completely abolished the induction of promoter activity in a concentration-dependent manner. In cells treated with LPS, IL-8 mRNA expression and secretion were induced and significantly reduced after co-treatment with OPs. TNF-α and IL-1β induced the expression and secretion of IL-8; however, OPs did not reduce these effects. Moreover, in the presence of IL-1β, OPs further increased IL-8 production. To gain further inside of the contradictory effect of OPs on NF-kB driven transcription and IL-8 expression in the presence of IL-1β, we evaluated IL-8 mRNA stability. OPs increased the IL-8 mRNA stability compared with the cell treated with IL-1β; this could account the increase of IL-8 production despite the inhibition of NF-kB signalling. Taken together these results indicate that OPs effects on expression and secretion of IL-8 depend on the inflammatory stimulus and suggest that OPs, in addition to NF-kB pathway, may act by other additional mechanisms on the inflammatory response in Caco-2 cells.