Olive oil polyphenols reduce oxysterols -induced redox imbalance and pro-inflammatory response in intestinal cells

Gessica Serra,Alessandra Incani,Gabriele Serreli,Laura Porru,M.Paola Melis,Carlo I.G Tuberoso,Daniela Rossin,Fiorella Biasi,Monica Deiana

doi:10.1016/j.redox.2018.05.006

Gessica Serra, Alessandra Incani + Show 7 more

Open Access

https://doi.org/10.1016/j.redox.2018.05.006

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Abstract

Dietary habits may strongly influence intestinal homeostasis. Oxysterols, the oxidized products of cholesterol present in cholesterol-containing foodstuffs, have been shown to exert pro-oxidant and pro-inflammatory effects, altering intestinal epithelial layer and thus contributing to the pathogenesis of human inflammatory bowel diseases and colon cancer. Extra virgin olive oil polyphenols possess antioxidant and anti-inflammatory properties, and concentrate in the intestinal lumen, where may help in preventing intestinal diseases. In the present study we evaluated the ability of an extra virgin olive oil phenolic extract to counteract the pro-oxidant and pro-inflammatory action of a representative mixture of dietary oxysterols in the human colon adenocarcinoma cell line (Caco-2) undergoing full differentiation into enterocyte-like cells. Oxysterols treatment significantly altered differentiated Caco-2 cells redox status, leading to oxidant species production and a decrease of GSH levels, after 1 h exposure, followed by an increase of cytokines production, IL-6 and IL-8, after 24 h. Oxysterol cell treatment also induced after 48 h an increase of NO release, due to the induction of iNOS. Pretreatment with the phenolic extract counteracted oxysterols effects, at least in part by modulating one of the main pathways activated in the cellular response to the action of oxysterols, the MAPK-NF-kB pathway. We demonstrated the ability of the phenolic extract to directly modulate p38 and JNK1/2 phosphorylation and activation of NF-kB, following its inhibitor IkB phosphorylation. The phenolic extract also inhibited iNOS induction, keeping NO concentration at the control level. Our results suggest a protective effect at intestinal level of extra virgin olive oil polyphenols, able to prevent or limit redox unbalance and the onset and progression of chronic intestinal inflammation.

Highlights

One of the main feature of chronic gastrointestinal inflammatory disorders, such as the inflammatory bowel diseases (IBD), is the overproduction of oxidant species, nitric oxide (NO) and pro-inflammatory cytokines and chemokines, secreted by enterocytes and local immune cells, which sustain and amplify inflammation and cause extensive damage to the mucosa [1,2]
The ability of the phenolic extract to modulate the oxysterols-induced pro-inflammatory effect in Caco-2 cells was evaluated measuring the production of IL-8, IL-6 and NO
A time-dependent increase of NO levels was found in the culture medium of oxysterols treated cells, showing a significant difference compared to control starting from 48 h of incubation

Summary

Introduction

One of the main feature of chronic gastrointestinal inflammatory disorders, such as the inflammatory bowel diseases (IBD), is the overproduction of oxidant species, nitric oxide (NO) and pro-inflammatory cytokines and chemokines, secreted by enterocytes and local immune cells, which sustain and amplify inflammation and cause extensive damage to the mucosa [1,2]. In previous studies we showed that they may Abbreviations: H2-DCFH-DA, 2′,7′-dichlorofluorescein diacetate; iNOS, inducible nitric oxide synthase; MAPK, mitogen activated protein kinase; NF-kB, nuclear factor kappa-light-chainenhancer of activated B cells; NO, nitric oxide; IBD, Inflammatory bowel diseases; NOX-1, NADPH oxidase isoform 1; GSH, reduced gluthatione; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; O2−, superoxide anion contribute to oxidative imbalance of the intestinal epithelium by inducing the generation of oxidant species [9,11], at least in part by upregulating intestinal NADPH oxidase isoform 1 (NOX-1); they are able to up regulate interleukin (IL)− 8 and IL-6 expression and synthesis [14] Their pro-inflammatory action seems to be mediated by the modulation of redox-sensible specific mitogen-activated protein kinase (MAPK) signaling pathways, and by activating redox-sensitive transcription nuclear factor kappa B (NF-kB) [15]

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