Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts.
Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts.
复制标题
DOI：
10.1152/ajpgi.1999.277.1.g245
复制
发表时间：
1999-07
期刊：
影响因子：
--
通讯作者：
E. V. van Tol;L. Holt;Fengling Li;Fenghua Kong;R. Rippe;M. Yamauchi;J. Pucilowska;P. Lund;And R Balfour Sartor;Van Tol;Eric A F;Ling Li;Jolanta Pucil-Owska;R. Balfour;Sartor
中科院分区：
文献类型：
--
作者：
E. V. van Tol;L. Holt;Fengling Li;Fenghua Kong;R. Rippe;M. Yamauchi;J. Pucilowska;P. Lund;And R Balfour Sartor;Van Tol;Eric A F;Ling Li;Jolanta Pucil-Owska;R. Balfour;Sartor
正常肠腔细菌和细菌细胞壁聚合物与慢性肠道炎症的发病机制有关。为了确定细菌及其产物对肠纤维化的直接参与，在从正常胎儿和慢性发炎的盲肠组织建立的肠肌成纤维细胞培养物中评价纯化的细菌细胞壁聚合物对胶原蛋白和细胞因子合成的影响。在这项研究中，刘易斯大鼠的肠壁内注射肽聚糖-多糖聚合物。胶原蛋白和转化生长因子（TGF）-β 1 mRNA水平进行了测定，并通过免疫组织化学与间充质细胞积累。在肠肌成纤维细胞培养物中评价细胞壁聚合物对纤维化细胞因子和胶原α 1（I型）表达的直接影响。我们发现，肠壁内注射细菌细胞壁聚合物诱导慢性肉芽肿性小肠结肠炎，胶原蛋白合成显著增加，TGF-β 1和白细胞介素（IL）-6表达随之增加。建立肠肌成纤维细胞培养物，其在表型和功能上都类似于参与体内纤维化的间充质细胞。细菌细胞壁聚合物直接刺激来自正常和炎症盲肠的肠肌成纤维细胞中胶原α 1（I）、TGF-β 1、IL-1 β和IL-6 mRNA的表达。内源性TGF-β 1的中和抑制体外胶原基因表达。从我们的结果中，我们得出结论，增加暴露于管腔细菌产物可以直接激活肠道间充质细胞，这些细胞在慢性肠道炎症区域积累，从而刺激遗传易感宿主的肠道纤维化。
Normal luminal bacteria and bacterial cell wall polymers are implicated in the pathogenesis of chronic intestinal inflammation. To determine the direct involvement of bacteria and their products on intestinal fibrogenesis, the effects of purified bacterial cell wall polymers on collagen and cytokine synthesis were evaluated in intestinal myofibroblast cultures established from normal fetal and chronically inflamed cecal tissues. In this study, the intestines of Lewis rats were intramurally injected with peptidoglycan-polysaccharide polymers. Collagen and transforming growth factor (TGF)-beta1 mRNA levels were measured and correlated with mesenchymal cell accumulation by immunohistochemistry. The direct effects of cell wall polymers on fibrogenic cytokine and collagen alpha1 (type I) expression were evaluated in intestinal myofibroblast cultures. We found that intramural injections of bacterial cell wall polymers induced chronic granulomatous enterocolitis with markedly increased collagen synthesis and concomitant increased TGF-beta1 and interleukin (IL)-6 expression. Intestinal myofibroblast cultures were established, which both phenotypically and functionally resemble the mesenchymal cells that are involved in fibrosis in vivo. Bacterial cell wall polymers directly stimulated collagen alpha1 (I), TGF-beta1, IL-1beta, and IL-6 mRNA expression in the intestinal myofibroblasts derived from both normal and inflamed cecum. Neutralization of endogenous TGF-beta1 inhibited in vitro collagen gene expression. From our results, we conclude that increased exposure to luminal bacterial products can directly activate intestinal mesenchymal cells, which accumulate in areas of chronic intestinal inflammation, thus stimulating intestinal fibrosis in genetically susceptible hosts.