Chitin microparticles for the control of intestinal inflammation.
Chitin microparticles for the control of intestinal inflammation.
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DOI：
10.1002/ibd.22874
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发表时间：
2012-09
影响因子：
4.9
通讯作者：
Mizoguchi, Emiko
中科院分区：
文献类型：
--
作者：
Nagatani, Katsuya;Wang, Sen;Llado, Victoria;Lau, Cindy W.;Li, Zongxi;Mizoguchi, Atsushi;Nagler, Cathryn R.;Shibata, Yoshimi;Reinecker, Hans-Christian;Mora, J. Rodrigo;Mizoguchi, Emiko
甲壳素是N-乙酰葡糖胺的聚合物，具有调节先天性和适应性免疫应答的能力。然而，几丁质介导的肠道炎症调节的详细机制仅部分已知。在这项研究中，甲壳素微粒（CMP）或PBS口服给药的急性和慢性结肠炎模型，每三天连续六周开始断奶年龄。在DSS诱导的结肠炎或TCRα敲除慢性结肠炎模型中，通过组织学、细胞因子产生、共培养研究和肠道细菌分析来评估这种治疗的效果。在组织学上，几丁质处理的小鼠在两种动物模型中与PBS处理的小鼠相比显示出显著抑制的结肠炎。与对照小鼠相比，几丁质处理小鼠的粘膜中IFNγ的产生上调。IFNγ产生细胞的主要来源是CD 4 + T细胞。在小鼠树突状细胞（DC）中，我们发现CMPs在48小时内被有效地内化和加工。从几丁质处理的小鼠中分离的肠系膜淋巴结（MLN）CD 4 + T细胞在与DC和几丁质共培养后的培养上清液中产生的IFNγ的量是对照组的7倍。与对照组相比，甲壳素处理的小鼠中MLN中CFSE低CD 4 + T细胞的增殖和肠道细菌易位率显著降低。此外，CMPs改善了肠道细菌组成的不平衡，并显著增加了非炎症结肠中产生IL-10的细胞，表明CMPs在肠粘膜中的免疫调节作用。总之，CMPs通过调节结肠中细胞因子平衡和微生物环境来显著抑制炎症的发展。
Chitin is a polymer of N-acetylglucosamine with the ability to regulate innate and adaptive immune responses. However, the detailed mechanisms of chitin-mediated regulation of intestinal inflammation are only partially known. In this study, Chitin-microparticles (CMPs) or PBS were orally administered to acute and chronic colitis models every three days for six consecutive weeks beginning at weaning age. The effects of this treatment were evaluated by histology, cytokine production, co-culture study and enteric bacterial analysis in DSS-induced colitis or TCRα knockout chronic colitis models. Histologically, chitin-treated mice showed significantly suppressed colitis as compared to PBS-treated mice in both animal models. The production of IFNγ was upregulated in the mucosa of chitin-treated mice compared to control mice. The major source of IFNγ-producing cells was CD4+ T cells. In mouse dendritic cells (DCs), we found that CMPs were efficiently internalized and processed within 48 hours. Mesenteric lymph nodes (MLNs) CD4+ T cells isolated from chitin-treated mice produced 7-fold higher amount of IFNγ in the culture supernatant after being co-cultured with DCs and chitin as compared to the control. Proliferation of CFSElow CD4+ T cells in MLNs and enteric bacterial translocation rates were significantly reduced in chitin-treated mice when compared to the control. In addition, CMPs improved the imbalance of enteric bacterial compositions and significantly increased IL-10-producing cells in non-inflamed colon, indicating the immunoregulatory effects of CMPs in intestinal mucosa. In conclusion, CMPs significantly suppress the development of inflammation by modulating cytokine balance and microbial environment in colon.
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影响因子：
5.5
作者：
Kogiso, Mari;Nishiyama, Akihito;Shibata, Yoshimi
通讯作者：
Shibata, Yoshimi
影响因子：
4.4
作者：
Da Silva, Carla A.;Chalouni, Cecile;Elias, Jack A.
通讯作者：
Elias, Jack A.
影响因子：
3.1
作者：
AUTENRIETH, IB;BEER, M;HEESEMANN, J
通讯作者：
HEESEMANN, J
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
32.4
作者：
Mizoguchi, A;Mizoguchi, E;Bhan, AK
通讯作者：
Bhan, AK