Intestinal anti-inflammatory activity of lentinan: influence on IL-8 and TNFR1 expression in intestinal epithelial cells.
Intestinal anti-inflammatory activity of lentinan: influence on IL-8 and TNFR1 expression in intestinal epithelial cells.
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DOI：
10.1371/journal.pone.0062441
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mizuno M
中科院分区：
文献类型：
--
作者：
Nishitani Y;Zhang L;Yoshida M;Azuma T;Kanazawa K;Hashimoto T;Mizuno M
炎症性肠病（IBD）的特征在于胃肠道的慢性炎症。β-1，3 1，6-葡聚糖是否能诱导免疫抑制作用尚不清楚。在这里，我们研究了香菇衍生的β-1，3 1，6-葡聚糖（称为香菇多糖）的肠道抗炎活性。用右旋糖酐硫酸钠（DSS）诱导的结肠炎小鼠来阐明香菇多糖在体内的作用。在细胞水平的评估中，香菇多糖被添加到由肠上皮Caco-2细胞和LPS刺激的巨噬细胞RAW 264. 7细胞组成的共培养模型中。采用肠袢结扎法研究香菇多糖对肠上皮细胞的影响。口服香菇多糖（100 μg/小鼠）显著改善DSS诱导的结肠炎，包括体重减轻、结肠长度缩短、组织学评分和炎症组织中炎性细胞因子mRNA表达。香菇多糖可降低Caco-2细胞白细胞介素（IL）-8 mRNA表达和核因子（NF）-κB活化，但不降低RAW264.7细胞产生肿瘤坏死因子（TNF）-α。流式细胞仪分析表明，表面水平的TNF受体（TNFR）1的香菇多糖治疗下降。网格蛋白介导的内吞抑制剂，单丹酰尸胺，取消香菇多糖抑制IL-8 mRNA的表达。香菇多糖在蛋白和mRNA水平上抑制Caco-2细胞TNFR 1的表达。香菇多糖还抑制小鼠IEC中TNFR 1 mRNA的表达。这些结果表明，香菇多糖通过抑制IL-8 mRNA的表达，抑制NF-κB的激活，这是由TNFR 1内吞和降低其在IEC中的表达触发的，从而表现出肠道抗炎活性。香菇多糖可能对治疗包括IBD在内的肠道炎症有效。
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. It is unknown whether β-1,3;1,6-glucan can induce immune suppressive effects. Here, we study intestinal anti-inflammatory activity of Lentinula edodes-derived β-1,3;1,6-glucan, which is known as lentinan. Dextran sulfate sodium (DSS)-induced colitis mice were used to elucidate effects of lentinan in vivo. In the cellular level assessment, lentinan was added into a co-culture model consisting of intestinal epithelial Caco-2 cells and LPS-stimulated macrophage RAW264.7 cells. Ligated intestinal loop assay was performed for assessing effects of lentinan on intestinal epithelial cells (IECs) in vivo. Oral administration of lentinan (100 µg/mouse) significantly ameliorated DSS-induced colitis in body weight loss, shortening of colon lengths, histological score, and inflammatory cytokine mRNA expression in inflamed tissues. Lentinan reduced interleukin (IL)-8 mRNA expression and nuclear factor (NF)-κB activation in Caco-2 cells without decreasing of tumor necrosis factor (TNF)-α production from RAW264.7 cells. Flow cytometric analysis revealed that surface levels of TNF receptor (TNFR) 1 were decreased by lentinan treatment. A clathrin-mediated endocytosis inhibitor, monodansylcadaverine, canceled lentinan inhibition of IL-8 mRNA expression. Moreover, lentinan inhibited TNFR1 expression in Caco-2 cells in both protein and mRNA level. Lentinan also inhibited TNFR1 mRNA expression in mouse IECs. These results suggest that lentinan exhibits intestinal anti-inflammatory activity through inhibition of IL-8 mRNA expression associated with the inhibition of NF-κB activation which is triggered by TNFR1 endocytosis and lowering of their expression in IECs. Lentinan may be effective for the treatment of gut inflammation including IBD.
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影响因子：
20.3
作者：
Gaultier, Alban;Arandjelovic, Sanja;Gonias, Steven L.
通讯作者：
Gonias, Steven L.
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B
DOI：
10.1073/pnas.0806585105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Chen, Nien-Jung;Chio, Iok In Christine;Mak, Tak W.
通讯作者：
Mak, Tak W.
影响因子：
4.9
作者：
Izutani, R;Loh, E Y;Macdermott, R P
通讯作者：
Macdermott, R P
影响因子：
5.4
作者：
Chin, YR;Horwitz, MS
通讯作者：
Horwitz, MS