Dietary Chitin Particles Called Mimetic Fungi Ameliorate Colitis in Toll-Like Receptor 2/CD14- and Sex-Dependent Manners.
Dietary Chitin Particles Called Mimetic Fungi Ameliorate Colitis in Toll-Like Receptor 2/CD14- and Sex-Dependent Manners.
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称为模拟真菌的膳食几丁质颗粒可通过 Toll 样受体 2/CD14 和性别依赖性方式改善结肠炎。
DOI：
10.1128/iai.00006-19
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发表时间：
2019
影响因子：
3.1
通讯作者：
Nan,Changlong
中科院分区：
文献类型：
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作者：
Louis,Patricia;Mercer,Brian;Cirone,AikoM;Johnston,Christina;Lee,ZacharyJ;Esiobu,Nwadiuto;Li,Zhongwei;Wei,Jianning;Dorey,CKathleen;Shibata,Yoshimi;Nan,Changlong
几丁质是一种天然的N-乙酰葡糖胺聚合物，是真菌细胞壁的主要结构成分。甲壳素具有粘膜粘附性;甲壳质微粒（CMP; 1- 10-μm直径）的抗炎作用已在炎症性肠病（IBD）模型中得到证实。本研究的目的是评估（i）在各种几丁质制剂中，CMP是否对雄性和雌性小鼠的结肠炎最有效，以及（ii）几丁质的抗炎作用是否需要宿主几丁质结合Toll样受体2（TLR 2）和CD 14。我们发现，CMP和大甲壳素珠（LCB; 40至70 μm）可改善雄性小鼠的结肠炎，但壳聚糖（脱乙酰甲壳素）微粒、寡糖甲壳素或氨基葡萄糖不能改善结肠炎。事实上，LCB比CMP更有效。另一方面，在女性结肠炎中，CMPs和LCB同样有效。当用LCB治疗时，TLR 2缺陷小鼠的性别都没有显示出抗炎作用。在CD 14缺乏的雄性或雌性动物中均未观察到LCB的抗炎作用。此外，一项体外研究表明，当LCB和CMP与胃酸哺乳动物几丁质酶（AMC）消化，其大小依赖性的巨噬细胞活化被修改，至少部分，这表明减少颗粒大小的饮食几丁质在胃中。有趣的是，男性胃AMC活性高于女性。我们的研究结果表明，饮食LCB是治疗结肠炎的最有效的准备在两种性别，这些抗炎作用的LCB是依赖于宿主TLR 2和CD 14。
Chitin is a naturalN-acetylglucosamine polymer and a major structural component of fungal cell walls. Dietary chitin is mucoadhesive; anti-inflammatory effects of chitin microparticles (CMPs; 1- to 10-μm diameters) have been demonstrated in models of inflammatory bowel disease (IBD). The goals of this study were to assess (i) whether CMPs among various chitin preparations are the most effective against colitis in male and female mice and (ii) whether host chitin-binding Toll-like receptor 2 (TLR2) and CD14 are required for the anti-inflammatory effect of chitin. We found that colitis in male mice was ameliorated by CMPs and large chitin beads (LCBs; 40 to 70 μm) but not by chitosan (deacetylated chitin) microparticles, oligosaccharide chitin, or glucosamine. In fact, LCBs were more effective than CMPs. In female colitis, on the other hand, CMPs and LCBs were equally and highly effective. Neither sex of TLR2-deficient mice showed anti-inflammatory effects when treated with LCBs. No anti-inflammatory effect of LCBs was seen in either CD14-deficient males or females. Furthermore, anin vitrostudy indicated that when LCBs and CMPs were digested with stomach acidic mammalian chitinase (AMC), their size-dependent macrophage activations were modified, at least in part, suggesting reduced particle sizes of dietary chitin in the stomach. Interestingly, stomach AMC activity was greater in males than females. Our results indicated that dietary LCBs were the most effective preparation for treating colitis in both sexes; these anti-inflammatory effects of LCBs were dependent on host TLR2 and CD14.