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首页> 外文期刊>Cellular immunology >Dietary oligosaccharides attenuate DSS-induced colitis in mice, induce PGlyRP3 expression, and inhibit NF-kappa B and MEK/ERK signaling (Retracted article. See vol. 362, 2021)
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Dietary oligosaccharides attenuate DSS-induced colitis in mice, induce PGlyRP3 expression, and inhibit NF-kappa B and MEK/ERK signaling (Retracted article. See vol. 362, 2021)

机译:膳食寡糖衰减小鼠中的DSS诱导的结肠炎,诱导pGlyrp3表达,抑制NF-Kappa B和MEK / ERK信号(缩回文章。见Vol.362,2021)

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摘要

Peptidoglycan recognition protein 3 (PGlyRP3) is a pattern recognition protein found in the gut epithelia and proven to have an anti-inflammatory effect in response to dietary lipids via the upregulation of PPAR gamma. We have reported an in vitro anti-inflammatory action for prebiotic oligosaccharides in the intestinal Caco-2 cells through stimulation of PPAR gamma and PGlyRP3. In the present study, this effect was examined in vivo in a DSS-induced colitis mouse model. Both Raftilose P95 and alpha 3-Sialyllactose oligosaccharides upregulated PGlyRP3 and showed an anti-colitis effect as evidenced by increased survival and reductions in body weight loss, bleeding in stool, diarrhea, and the expression of the cytokine genes IL6, IL1b and TNF alpha. However, unlike the in vitro results, the role of PPAR gamma was unclear; both oligosaccharides could upregulate neither PPAR gamma gene nor protein expressions, nor the administration of its inhibitor BADGE could affect the upregulation of PGlyRP3 in response to oligosaccharides. Instead, phosphoimmunoblotting indicated that both oligosaccharides inhibit the phosphorylation of MEK1/2 and ERK1/2 caused by DSS. Also, both oligosaccharides reversed the DSS-induced downregulation in the gene expression of I kappa B alpha, the upregulation of NF kappa B1 and cox2, and the decrease of the cytoplasmic (inactive) NF-kappa B p65 protein that indicates its transformation to the (active) inflammatory nuclear form. The present study showed that the prebiotic oligosaccharides Raftilose P95 and alpha 3-Sialyllactose have an anti-colitis effect in mice through the induction of PGlyRP3 expression and down-regulation of the MEK/ERK and the NF-kappa B inflammatory pathways.
机译:肽聚糖识别蛋白3(PGlyRP3)是一种在肠道上皮中发现的模式识别蛋白,经证明通过上调PPARγ对饮食脂质具有抗炎作用。我们已经报道了通过刺激PPARγ和PGlyRP3对肠道Caco-2细胞中的益生元低聚糖的体外抗炎作用。在本研究中,在DSS诱导的结肠炎小鼠模型中检测了这种作用。Raftilose P95和alpha 3-唾液酸乳糖低聚糖均上调PGlyRP3,并显示出抗结肠炎的效果,其表现为存活率增加,体重减轻、大便出血、腹泻以及细胞因子基因IL6、IL1b和TNF-α的表达减少。然而,与体外结果不同,PPARγ的作用尚不清楚;两种寡糖均不能上调PPARγ基因或蛋白质表达,其抑制剂BADGE的施用也不能影响PGlyRP3对寡糖的反应上调。相反,磷酸化免疫印迹显示,这两种寡糖都能抑制DSS引起的MEK1/2和ERK1/2的磷酸化。此外,这两种低聚糖都逆转了DSS诱导的IκBα基因表达下调、NFκB1和cox2的上调,以及胞质(非活性)NFκB p65蛋白的降低,表明其转化为(活性)炎性核形式。目前的研究表明,益生元低聚糖Raftilose P95和α3-唾液酸乳糖通过诱导PGlyRP3表达和下调MEK/ERK和NF-κB炎症途径在小鼠中具有抗结肠炎作用。

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