Lipopolysaccharide-Induced Increase in Intestinal Epithelial Tight Permeability Is Mediated by Toll-Like Receptor 4/Myeloid Differentiation Primary Response 88 (MyD88) Activation of Myosin Light Chain Kinase Expression

Nighot, Meghali; Al–Sadi, Rana; Guo, Shuzhen; Rawat, Manmeet; Nighot, Prashant K.; Watterson, Martin D.; Thomas, Y.

doi:10.1016/j.ajpath.2017.08.005

Cited by 165 publications

(138 citation statements)

References 55 publications

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“…TLR-mediated signaling pathways are involved in regulating intestinal epithelial barrier integrity [60]. In our study, NE infection significantly increased IFN-γ and IGF-2 mRNA levels and downregulated TLR-4, adaptor protein tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF-6), NF-κB, TNFSF15, TLR-activating negative regulators TOLLIP, PI3K and SOCS-6 and EGFR mRNA expression in the jejunum compared with the unchallenged control.…”

Section: Discussionmentioning

confidence: 55%

Dietary encapsulated essential oils and organic acids mixture improves gut health in broiler chickens challenged with necrotic enteritis

Pham

Kan

Huang³

et al. 2020

J Animal Sci Biotechnol

102

101

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Background: The poultry industry is in need of effective antibiotic alternatives to control outbreaks of necrotic enteritis (NE) due to Clostridium perfringens. In the present study, we investigated the effects of dietary supplementation with a blend of encapsulated essential oils and organic acids (BLJ) on growth performance and gut health using a coinfection model of NE in broiler chickens. Methods: Two hundred and eighty-eight one-day-old male Arbor Acres broiler chicks were randomly assigned using a 2 × 2 factorial design into two groups fed either 0 or 500 mg/kg dietary BLJ and co-challenged (or not challenged for the control) with Eimeria spp./C. perfringens. Results: Infected birds fed the BLJ-supplemented diet exhibited an improved feed conversion ratio throughout the trial (P < 0.01), a higher villus height and villus height/crypt depth ratio, and reduced intestinal C. perfringens counts, liver C. perfringens carriage, gut lesion scores and serum fluorescein isothiocyanate dextran (FITC-D) concentrations at 7 d postinfection compared with those of birds without BLJ supplementation (P < 0.05). NE-infected birds fed BLJ exhibited significantly upregulated claudin-1 and IGF-2 mRNA levels (P < 0.05), increased A20 mRNA expression and significantly downregulated TRAF-6, TNFSF15 and TOLLIP mRNA levels in the jejunum at 7 d post-infection compared with those in birds without BLJ supplementation (P < 0.05). Compared with the uninfected and untreated birds, the uninfected birds fed BLJ displayed increased relative abundances of Lactobacillus and Coprococcus but reduced Rikenellaceae levels. Compared with the unsupplemented NE-challenged birds, infected birds fed BLJ showed an increased relative abundance of Unclassified_ Lachnospiraceae and a significantly decreased relative abundance of Erysipelotrichaceae. Conclusion: BLJ supplementation improved growth performance and gut health in NE-infected broiler chickens by strengthening the intestinal barrier function, positively modulating the gut microbiota community and differentially regulating intestinal immune responses. Our results also suggested that adding BLJ effectively controlled NE infections after experimental Eimeria and Clostridium perfringens coinfection.

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Section: Discussionmentioning

confidence: 55%

Dietary encapsulated essential oils and organic acids mixture improves gut health in broiler chickens challenged with necrotic enteritis

Pham

Kan

Huang³

et al. 2020

J Animal Sci Biotechnol

102

101

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“…ethanol administration and the presence of bacterial products such as LPS, since both are TLR4 agonists. Recent studies suggest that physiologically relevant concentrations of LPS (0–1 ng·mL −1 ) cause an increase in colonic epithelial TJ permeability that was mediated by the up‐regulation of myosin light‐chain kinase in a mechanism dependent on the TLR‐4/MyD88 signal transduction pathway (Nighot et al ., ). Both long‐term (Tamai et al ., ) and acute ethanol administration (Tamai et al ., ) enhance small intestine absorption of LPS, and we demonstrated that this also occurs after repeated binge episodes (Antón et al ., and current study).…”

Section: Discussionmentioning

confidence: 97%

Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide

Antón

Rodríguez-González

Ballesta

et al. 2018

British J Pharmacology

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The authors contributed equally to this work. BACKGROUND AND PURPOSEChronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure and the ability of the biolipid oleoylethanolamide (OEA) to prevent ethanol binge-induced intestinal barrier dysfunction. EXPERIMENTAL APPROACHOEA was injected i.p. before repeated ethanol administration by oral gavage. Plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load. Immune/inflammatory parameters, TJ proteins and apoptotic markers were determined in colonic tissue by RT-PCR and Western blotting. TJ ultrastructure was examined by transmission electron microscopy. KEY RESULTSEthanol binges induced bacterial translocation to the MLN (mainly) and spleen. Colonic tissues showed signs of inflammation, and activation of innate (Toll-like receptor-4) and adaptive (IgA) immune systems and TJ proteins (occludin and claudin-3) were decreased after ethanol binges. Pretreatment with OEA reduced intestinal inflammation and immune activation and partially preserved the TJ structure affected by alcohol binges but had no effect on alcohol-induced apoptosis. Ultrastructural analyses of colonic TJs revealed dilated TJs in all ethanol groups, with less electron-dense material in non-pretreated rats. The protective effects of i.p. OEA did not reduce bacterial translocation to the MLN. However, intragastric OEA administration significantly reduced plasma LPS levels and bacterial translocation to the MLN. CONCLUSION AND IMPLICATIONSOEA-based pharmacotherapies could potentially be useful to treat disorders characterized by intestinal barrier dysfunction, including alcohol abuse.

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“…In humans, dysfunction of intestinal epithelial barrier leads to increased permeability of intestinal mucosa, subsequent translocation of intestinal pathogenic bacteria or toxins, which in turn aggravates the damage of intestinal barrier integrity, resulting in local intestinal or systemic disease such as inflammatory bowel diseases, multiple organ dysfunction syndromes, and sepsis (Yoseph et al, 2016;Meng et al, 2017). LPS, a representative biological marker of systemic microbial translocation, plays an important role in the initiation and development of intestinal epithelial barrier dysfunction (Nighot et al, 2017). Caco-2 cells infected with LPS are widely used as an in vitro model for evaluating intestinal barrier function in humans.…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

Guo

Zhao

et al. 2020

Front. Pharmacol.

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Intestinal barrier dysfunction is an important clinical problem in various acute and chronic pathological conditions. Ferulic acid (FA) can attenuate the intestinal epithelial barrier dysfunction, however, the underlying mechanism remains unclear. The present study aimed to uncover the protective effect of FA on intestinal epithelial barrier dysfunction in a Caco-2 cell model of lipopolysaccharide (LPS) stimulation and the underlying mechanism. Caco-2 cells were pretreated with FA and then exposed to LPS stimulation. The barrier function of Caco-2 cells was evaluated by measuring trans-epithelial resistance (TER) and 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4) flux, and analyzing the tight junction protein expression and structure. The results showed that decreased TER and increased FITC-FD4 flux were observed in Caco-2 cells stimulated with LPS, but these effects were attenuated by FA pretreatment. FA pretreatment inhibited LPS-induced decrease in occludin and ZO-1 mRNA and protein expression. LPS stimulation decreased miR-200c-3p expression, whereas this decrease was inhibited by FA pretreatment. Furthermore, overexpression of miR-200c-3p strengthened the protective effects of FA on LPS-induced Caco-2 cell barrier dysfunction by decreasing epithelial permeability, increasing occludin and ZO-1 protein expression, and maintaining of ZO-1 protein distribution, while suppression of miR-200c-3p reversed the protective effects of FA. LPS treatment increased the expression of PTEN protein and decreased expression of phosphorylated PI3K and AKT proteins. However, pretreatment of FA inhibited expression of PTEN protein and promoted activation of PI3K/AKT signaling pathway in the LPS-treated Caco-2 cells, and this regulatory effect of FA on the PTEN/PI3K/AKT signaling pathway was strengthened or weakened by miR-200c-3p overexpression or suppression, respectively. Our findings suggested that in Caco-2 cells, FA promotes activation of PI3K/AKT pathway by miR-200c-3p-mediated suppression of the negative

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Lipopolysaccharide-Induced Increase in Intestinal Epithelial Tight Permeability Is Mediated by Toll-Like Receptor 4/Myeloid Differentiation Primary Response 88 (MyD88) Activation of Myosin Light Chain Kinase Expression

Cited by 165 publications

References 55 publications

Dietary encapsulated essential oils and organic acids mixture improves gut health in broiler chickens challenged with necrotic enteritis

Dietary encapsulated essential oils and organic acids mixture improves gut health in broiler chickens challenged with necrotic enteritis

Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

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