Abstract

We revisited the action of a carotenoid, the lycopene, on the expression of proinflammatory genes, reactive oxygen species (ROS) production, and metalloprotease (MMP9) activity. THP1 and Caco2 cell lines were used as in vitro models for the two main cell types found in intestine tissue, that is, monocytes and epithelial cells. Proinflammatory condition was induced using either phorbol ester acetate (PMA), lipopolysaccharide (LPS) or tumor necrosis factor (TNF). In THP1 cells, short term pretreatment (2 h) with a low concentration (2 μM) of lycopene reinforce proinflammatory gene expression. The extent of the effect of lycopene is dependent on the proinflammtory stimulus (PMA, LPS or TNF) used. Lycopene enhanced MMP9 secretion via a c-AMP-dependent process, and reduced ROS production at higher concentrations than 2 μM. Cell culture media, conditioned by PMA-treated monocytes and then transferred on CaCo-2 epithelial cells, induced a proinflammatory state in these cells. The extent of this inflammatory effect was reduced when cells has been pretreated (12 h) with lycopene. At low concentration (2 μM or less), lycopene appeared to promote an inflammatory state not correlated with ROS modulation. At higher concentration (5 μM–20 μM), an anti-inflammatory effect takes place as a decrease of ROS production was detected. So, both concentration and time have to be considered in order to define the exact issue of the effect of carotenoids present in meals.

Highlights

  • Epidemiological studies have shown that increased consumption of fruit and vegetables is associated with a lower risk of several kinds of pathologies [1,2,3]

  • We investigated the effects of physiological concentration (2 μM) of lycopene on monocyte and an intestine-derived epithelial cell lines, on various proinflammatory targets, that is, reactive oxygen species (ROS) production, transcription of cytokines, and MMP9 as well as MMP9 activities

  • The following compounds were from Sigma (L’Isle d’Abeau, France): phosphatebuffered saline (PBS), bovine serum albumin (BSA), phenylmethylsulfonyl fluoride (PMSF), iodoacetamide, aprotinin, leupeptin, peptatin, o-phenanthroline, DEAEdextran, 4-methyl-umbelliferyl-β-D-galactoside (MUG), phorbol myristate acetate (PMA), vitamin D3 (VD3), retinoıc acid (AR), lucigenin, lycopene, interferon γ (IFNγ), Tumor Necrosis Factor α (TNFα), N-(Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL12,330A) and E

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Summary

Introduction

Epidemiological studies have shown that increased consumption of fruit and vegetables is associated with a lower risk of several kinds of pathologies [1,2,3]. Such beneficial effect could be due at least in part to the presence of carotenoids in the diet. There is evidence suggesting that this compound plays a role in decreasing the occurrence of and the progression of certain cancers (prostate and hepatoma) [4,5,6,7] and several epidemiological studies have linked high plasma lycopene concentrations to a lower risk of developing cardiovascular disease [4]. The mechanism underlying these effects remains unknown and there is debate over the impact of lycopene on human health [1,2,3]

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