Derangement of intestinal epithelial cell monolayer by dietary cholesterol oxidation products

Deiana, Monica; Calfapietra, Simone; Incani, Alessandra; Atzeri, Angela; Rossin, Daniela; Loi, Roberto; Sottero, Barbara; Iaia, Noemi; Poli, Giuseppe; Biasi, Fiorella

doi:10.1016/j.freeradbiomed.2017.10.390

Cited by 30 publications

(35 citation statements)

References 48 publications

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“…Dietary habits may reduce or increase the inflammatory process linked to intestinal unbalance and damage that may lead to IBD initiation and progression. The ingestion of cholesterol oxidized products has been recently considered among the risk factors associated to the pathogenesis of IBD, being able to alter intestinal epithelial cells homeostasis [10] , [11] , [31] , [32] towards a pro-inflammatory phenotype. Our data support the hypothesis of a direct pro-inflammatory effect of dietary oxysterols on intestinal Caco-2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Oxysterols present in food are the oxidized products of dietary cholesterol and have been reported to reach concentrations ranging from 10 to 100 μM [7] , [8] . They have been shown to potentially interfere with the homeostasis of the human digestive tract, by promoting and sustaining irreversible damage and dysfunction of the colonic epithelial barrier, as demonstrated in vitro [9] , [10] , which may lead to IBD [11] and colon cancer [12] , [13] . In previous studies we showed that they may contribute to oxidative imbalance of the intestinal epithelium by inducing the generation of oxidant species [9] , [11] , at least in part by up-regulating intestinal NADPH oxidase isoform 1 (NOX-1); they are also able to up regulate interleukin (IL)− 8 and IL-6 expression and synthesis [14] .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…Intestinal mechanical barrier is mainly composed of intestinal mucosal epithelial cells and intercellular connection [ 18 ]. And the intestinal mechanical barrier transmembrane proteins ZO-1 and occludin are important structures that make up a tight junction, which determines the permeability of the intestinal barrier and intestinal tract [ 19 ]. Once the transmembrane proteins are reduced, missed, or mutated, the intestinal epithelial cell permeability would increase [ 20 ], and bacteria, lipopolysaccharides, and macromolecules would enter the systemic circulation through tight junctions [ 21 , 22 ], resulting in local or systemic inflammatory responses that can lead to MODS, even caused death [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Protective Mechanism of CAY10683 on Intestinal Mucosal Barrier in Acute Liver Failure through LPS/TLR4/MyD88 Pathway

Wang

Chen

et al. 2018

Mediators of Inflammation

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The purpose of this study was to investigate the protective mechanism of HDAC2 inhibitor CAY10683 on intestinal mucosal barrier in acute liver failure (ALF). In order to establish ALF-induced intestinal epithelial barrier disruption models, D-galactosamine/LPS and LPS were, respectively, used with rats and NCM460 cell and then administrated with CAY10683. Transepithelial electrical resistance (TEER) was measured to detect the permeability of cells. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels. The intestinal epithelial tissue pathology was detected. After interfering with CAY10683, the mRNA and protein levels of TLR4, MyD88, TRIF, and TRAF6 were decreased compared with model group (P < 0.05), whereas the levels of ZO-1 and occluding were elevated (P < 0.05). The permeability was elevated in CAY10683-interfered groups, when compared with model group (P < 0.05). And the degree of intestinal epithelial tissue pathological damage in CAY10683 group was significantly reduced. Moreover, CAY10683 significantly decreased the TLR4 staining in animal tissue. The HDAC2 inhibitor CAY10683 could promote the damage of intestinal mucosal barrier in ALF through inhibiting LPS/TLR4/MyD88 pathway.

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“…There is growing evidence indicating that cholesterol auto-oxidation products, namely oxysterols, can promote and stimulate intestinal inflammatory diseases with proinflammatory properties and by inducing epithelial barrier disturbance. A recent study showed the ability of a combination of dietary auto-oxidation oxysterols to induce the loss of intestinal epithelial layer integrity in monolayers of differentiated CaCo-2 cells [47], with subsequent hyperactivation of pro-inflammatory cytokines matrix metalloproteinases (MMP)-2 and -9 and decreased levels of tight junction proteins including ZO-1, occludin, and junction adhesion molecule-A (JAM-A). Therefore, inflammation could exacerbate barrier dysfunction in a synergistic manner.…”

Section: Discussionmentioning

confidence: 99%

27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction

Wang

et al. 2020

J Neuroinflammation

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Background: Research on the brain-gut-microbiota axis has led to accumulating interest in gut microbiota dysbiosis and intestinal barrier dysfunction in Alzheimer's disease (AD). Our previous studies have demonstrated neurotoxic effects of 27-hydroxycholesterol (27-OHC) in in vitro and in vivo models. Here, alterations in the gut microbiota and intestinal barrier functions were investigated as the possible causes of cognitive deficits induced by 27-OHC treatment. Methods: Male APP/PS1 transgenic and C57BL/6J mice were treated for 3 weeks with 27-OHC (5.5 mg/kg/day, subcutaneous injection) and either a 27-OHC synthetase inhibitor (anastrozole, ANS) or saline. The Morris water maze and passive avoidance test were used to assess cognitive impairment. Injuries of the intestine were evaluated by histopathological examination. Intestinal barrier function was assessed by plasma diamine oxidase (DAO) activity and D-lactate. Systemic and intestinal inflammation were evaluated by IL-1β, TNF-α, IL-10, and IL-17 concentrations as determined by ELISA. The fecal microbiome and short-chain fatty acids (SCFAs) were analyzed using 16S rDNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Tight junction proteins were evaluated in the ileum and colon by qRT-PCR and Western blots. Tight junction ultrastructure was examined by transmission electron microscopy. Results: Treatment with 27-OHC resulted in severe pathologies in the ileum and colon. There was impaired intestinal barrier integrity as indicated by dilated tight junctions and downregulation of tight junction proteins, including occludin, claudin 1, claudin 5, and ZO-1, and signs of inflammation (increased IL-1β, TNF-α, and IL-17). Fecal 16S rDNA sequencing and taxonomic analysis further revealed a decreased abundance of Roseburia and reduced fecal levels of several SCFAs in 27-OHC-treated mice. Meanwhile, co-treatment with ANS reduced intestinal inflammation and partially preserved intestinal barrier integrity in the presence of 27-OHC.

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Derangement of intestinal epithelial cell monolayer by dietary cholesterol oxidation products

Cited by 30 publications

References 48 publications

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

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

The Protective Mechanism of CAY10683 on Intestinal Mucosal Barrier in Acute Liver Failure through LPS/TLR4/MyD88 Pathway

27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction

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