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 PPARγ. We have reported an in vitro anti-inflammatory action for prebiotic oligosaccharides in the intestinal caco2 cells through stimulation of PPARγ and PGlyRP3. In the present study, this effect was examined in vivo in a DSS-induced colitis mouse model. Both Raftilose P95 and α3-Sialyllactose oligosaccharides, via the upregulation of PGlyRP3, 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 TNFα. However, unlike the in vitro results, the role of PPARγ was absent, since both oligosaccharides could upregulate neither PPARγ 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 IκBα, the upregulation of NFκB1 and cox2, and the decrease of the cytoplasmic (inactive) NF-κB p65 protein that indicates its transformation to the (active) inflammatory nuclear form. The present study showed that the prebiotic oligosaccharides have anti-colitis effect in mice via activation of PGlyRP3, which renders anti-inflammatory effect through inhibition of the MEK/ERK and the NF-κB inflammatory pathways, rather than the activation of PPARγ anti-inflammatory action.

肽聚糖识别蛋白 3 (PGlyRP3) 是一种在肠道上皮细胞中发现的模式识别蛋白，经证明可通过上调 PPARγ 对膳食脂质产生抗炎作用。我们已经报道了通过刺激 PPARγ 和 PGlyRP3 对肠道 caco2 细胞中的益生元寡糖具有体外抗炎作用。在本研究中，这种效应在 DSS 诱导的结肠炎小鼠模型中进行了体内检查。Raftilose P95 和 α3-Sialyllactose 寡糖都通过上调 PGlyRP3 显示出抗结肠炎作用，这可以通过增加存活率和减少体重减轻、大便出血、腹泻以及细胞因子基因IL6、IL1b和肿瘤坏死因子α。然而，与体外结果不同，PPARγ 的作用不存在，因为两种寡糖都不能上调 PPARγ 基因和蛋白质表达，其抑制剂 BADGE 的给药也不会影响 PGlyRP3 对寡糖的反应上调。相反，磷酸免疫印迹表明两种寡糖都抑制 DSS 引起的 MEK1/2 和 ERK1/2 的磷酸化。此外，两种寡糖都逆转了 DSS 诱导的IκBα基因表达下调、 NFκB1和cox2的上调，以及细胞质（非活性）NF-κB p65 蛋白的减少，表明其转化为（活性）炎性核形式。本研究表明，益生元寡糖通过激活 PGlyRP3 对小鼠具有抗结肠炎作用，PGlyRP3 通过抑制 MEK/ERK 和 NF-κB 炎症通路而不是激活 PPARγ 来发挥抗炎作用。行动。