Butyrate Suppression of Colonocyte NF-κB Activation and Cellular Proteasome Activity

Yin, Lei; Laevsky, Gary; Giardina, Charles

doi:10.1074/jbc.m105170200

Cited by 248 publications

(161 citation statements)

References 80 publications

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“…However, the underlying mechanisms seem to depend on the cell type investigated and include on the one hand an HDAC-inhibitor-mediated continual degradation of de novo synthesised IκBα protein (possibly by prolonged activation of the upstream IκB-kinase) causing prolonged presence and DNA-binding of NFκB in the nucleus and enhancing NFκB-dependent transactivation, or on the other hand a reduction in proteasomal degradation of IκBα, preventing NFκB nuclear translocation and DNA binding [4,8,[46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells

et al. 2007

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Aims/hypothesis The immune-mediated elimination of pancreatic beta cells in type 1 diabetes involves release of cytotoxic cytokines such as IL-1β and IFNγ, which induce beta cell death in vitro by mechanisms that are both dependent and independent of nitric oxide (NO). Nuclear factor kappa B (NFκB) is a critical signalling molecule in inflammation and is required for expression of the gene encoding inducible NO synthase (iNOS) and of proapoptotic genes. NFκB has recently been shown to associate with chromatin-modifying enzymes histone acetyltransferases and histone deacetylases (HDAC), and positive effects of HDAC inhibition have been obtained in several inflammatory diseases. Thus, the aim of this study was to investigate whether HDAC inhibition protects beta cells against cytokine-induced toxicity. Materials and methods The beta cell line, INS-1, or intact rat islets were precultured with HDAC inhibitors suberoylanilide hydroxamic acid or trichostatin A in the absence or presence of IL-1β and IFNγ. Effects on insulin secretion and NO formation were measured by ELISA and Griess reagent, respectively. iNOS levels and NFκB activity were measured by immunoblotting and by immunoblotting combined with electrophoretic mobility shift assay, respectively. Viability was analysed by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and apoptosis by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and histone-DNA complex ELISA. Results HDAC inhibition reduced cytokine-mediated decrease in insulin secretion and increase in iNOS levels, NO formation and apoptosis. IL-1β induced a bi-phasic phosphorylation of inhibitor protein kappa Bα (IκBα) with the 2nd peak being sensitive to HDAC inhibition. No effect was seen on IκBα degradation and NFκB DNA binding. Conclusions/interpretation HDAC inhibition prevents cytokine-induced beta cell apoptosis and impaired beta cell function associated with a downregulation of NFκB transactivating activity.

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Section: Discussionmentioning

confidence: 99%

Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells

et al. 2007

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“…In agreement with previous reports, Nabutyrate resulted in a higher expression of MCT1, whereas TNF-a had an inhibitory effect (13,16) . Butyrate has antiinflammatory properties in human intestinal epithelial cells, which is probably mediated by the inhibition of the NF-kB pathway (33,34) . Furthermore, colonic and systemic immunoreactivity was reduced after a long-term feeding experiment with resistant starch in pigs, possibly due to an increased luminal concentration of butyrate (35) .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

et al. 2015

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The present study investigated the influence of bacterial metabolites on monocarboxylate transporter 1 (MCT1) expression in pigs using in vivo, ex vivo and in vitro approaches. Piglets (n 24) were fed high-protein (26 %) or low-protein (18 %) diets with or without fermentable carbohydrates. Colonic digesta samples were analysed for a broad range of bacterial metabolites. The expression of MCT1, TNF-a, interferon g (IFN-g) and IL-8 was determined in colonic tissue. The expression of MCT1 was lower and of TNF-a and IL-8 was higher with high-protein diets (P, 0·05). MCT1 expression was positively correlated with L-lactate, whereas negatively correlated with NH 3 and putrescine (P,0·05). The expression of IL-8 and TNF-a was negatively correlated with L-lactate and positively correlated with NH 3 and putrescine, whereas the expression of IFN-g was positively correlated with histamine and 4-ethylphenol (P,0·05). Subsequently, porcine colonic tissue and Caco-2 cells were incubated with Na-butyrate, NH 4 Cl or TNF-a as selected bacterial metabolites or mediators of inflammation. Colonic MCT1 expression was higher after incubation with Na-butyrate (P,0·05) and lower after incubation with NH 4 Cl or TNF-a (P,0·05). Incubation of Caco-2 cells with increasing concentrations of these metabolites confirmed the up-regulation of MCT1 expression by Na-butyrate (linear, P, 0·05) and down-regulation by TNF-a and NH 4 Cl (linear, P,0·05). The high-protein diet decreased the expression of MCT1 in the colon of pigs, which appears to be linked to NH 3 -and TNF-a-mediated signalling.

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“…In addition, BuA has been shown to modulate the activity of the transcription factor NF-jB in a number of different cell types, including colon cancer cells [27]. The ability of BuA to modulate NF-jB activity may arise from its ability to inhibit histone deacetylases.…”

mentioning

confidence: 99%

Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require activation of CAD and downregulation of VEGF

Belakavadi

Prabhakar

Salimath

2005

Biochemical and Biophysical Research Communications

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Butyrate Suppression of Colonocyte NF-κB Activation and Cellular Proteasome Activity

Cited by 248 publications

References 80 publications

Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells

Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require activation of CAD and downregulation of VEGF

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