Dietary anti-inflammatory chitin in colitis

结肠炎中膳食抗炎甲壳素

• 批准号: 8686392
• 负责人: YOSHIMI SHIBATA
• 金额: $ 38.06万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8686392
• 关键词: Animals; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Binding; Binding Proteins; CD44 gene; Cardiovascular Diseases; Cells; Chitin; Chitosan; Chronic; Citrobacter rodentium; Clinical Research; Colitis; Colon; Colorectal Cancer; Complementary and alternative medicine; Development; Diet; Disease; Epithelial Cells; Figs - dietary; Fistula; Glucosamine; Goals; Human; Immunology; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intestinal Diseases; Intestines; Knowledge; Literature; Measures; Methods; Modeling; Modification; Monitor; Morbidity - disease rate; Mus; Obstruction; Oral; Oral Administration; Pharmaceutical Preparations; Play; Polymers; Preparation; Protocols documentation; Relapse; Research; Research Project Grants; Risk; Role; Signal Transduction; Testing; Therapeutic; Therapeutic Effect; Toll-Like Receptor 2; Toxic effect; Translating; Translations; United States; Work; base; cancer prevention; clinically relevant; enteropathogenic Escherichia coli; graduate student; gut microbiota; improved; intestinal epithelium; macrophage; microorganism interaction; prevent; public health relevance; receptor binding; research clinical testing; response; tool; treatment strategy; undergraduate student

DESCRIPTION (provided by applicant): Inflammatory bowel disease (IBD) is a chronic relapsing colitis, associated with risk for obstruction, fistula and colorectal cancer. It is probaly caused by immunologically dysregulated host and microbial interactions. Effective anti-inflammatory medications are associated with toxicities, so new treatment strategies for IBD are needed. Dietary glucosamine, widely used for arthritis, cardiovascular disease, and cancer prevention, is suggested as a therapy for IBD. We and others have shown that colonic inflammation in mice is suppressed by oral administration of chitin, a natural glucosamine polymer derivative. The efficacy depends on the specific form of chitin, available as soluble chitin, chitin microparticles at 1 - 10 ?m (CMPs), large chitin beads at 40 - 100 ?m (LCBs), chitosan microparticles at 1 - 10 ?m (CsMPs) and soluble chitosan. We propose to determine which chitin preparation is the most effective in suppressing colitis activities. Oral chitin may induce responses by intestinal epithelial cells and/or colonic macrophages through their chitin binding proteins (CBPs), including toll-like receptor 2 (TLR2) and CD44. These two CBPs are reasonable targets for chitin treatment since they are known to be anti- and pro-inflammatory in mouse colitis, and seem to functionally down-regulate each other. Based on our preliminary results, we hypothesize that chitin preparations optimal for anti-colitis effects will up-regulate TLR2 and down-regulate CD44 activities, and protect intestinal epithelia. To test the hypothesis, we will determine the chitin form(s) that ameliorate colitis in mice infected with Citrobacter rodentium as a model of human IBD caused by enteropathogenic Escherichia coli. We will measure TLR2 and CD44 levels in the colon epithelial cells and colon macrophages to assess whether these CBP activities are associated with a shift in normal gut microbiota. Next, using mice deficient of TLR2 and CD44, we will determine whether TLR2 and CD44 are responsible for amelioration of colitis by the optimal chitin form selected above. The knowledge gained from this work will apply to the establishment of defined anti-colitis therapeutic protocol translating o clinical studies of IBD and possibly extended to other diseases where CBPs have been predicted to play key inflammatory roles. Furthermore, it will engage graduate and undergraduate students in clinically-relevant immunology research, encouraging their scientific development and giving them a deeper appreciation of complementary and alternative medicines.

描述（由申请人提供）：炎症性肠病（IBD）是一种慢性复发性结肠炎，与梗阻、瘘管和结直肠癌的风险相关。它可能是由免疫失调的宿主和微生物相互作用引起的。有效的抗炎药物与毒性相关，因此需要新的IBD治疗策略。膳食葡萄糖胺，广泛用于关节炎，心血管疾病和癌症预防，被建议作为治疗IBD。我们和其他人已经证明，口服几丁质（一种天然氨基葡萄糖聚合物衍生物）可以抑制小鼠的结肠炎症。功效取决于甲壳素的具体形式，可作为可溶性甲壳素，甲壳素微粒在1 - 10 ？m (CMPs)，大甲壳素珠在40 - 100 ？m (LCBs)，壳聚糖微粒在1 - 10 ？m （CsMPs）和可溶性壳聚糖。我们建议确定哪种几丁质制剂对抑制结肠炎活性最有效。口服几丁质可通过其几丁质结合蛋白（CBPs），包括toll样受体2 （TLR2）和CD44，诱导肠上皮细胞和/或结肠巨噬细胞的应答。这两种CBPs是几丁质治疗的合理靶点，因为已知它们在小鼠结肠炎中具有抗炎和促炎作用，并且似乎在功能上相互下调。基于我们的初步研究结果，我们假设抗结肠炎效果最佳的几丁质制剂可以上调TLR2，下调CD44活性，保护肠上皮。为了验证这一假设，我们将确定几丁质形式，这些几丁质形式可以改善啮齿柠檬酸杆菌感染小鼠的结肠炎，作为肠致病性大肠杆菌引起的人类IBD模型。我们将测量结肠上皮细胞和结肠巨噬细胞中的TLR2和CD44水平，以评估这些CBP活动是否与正常肠道微生物群的改变有关。接下来，使用TLR2和CD44缺失的小鼠，我们将确定TLR2和CD44是否通过上述选择的最佳几丁质形式改善结肠炎。从这项工作中获得的知识将适用于建立明确的抗结肠炎治疗方案，转化为IBD的临床研究，并可能扩展到其他疾病，其中CBPs已被预测在炎症中起关键作用。此外，它将吸引研究生和本科生参与临床相关的免疫学研究，鼓励他们的科学发展，并让他们更深入地了解补充和替代药物。

项目成果

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity.

急性有氧运动对肥胖中几丁质酶 3 样蛋白 1 和 intelectin-1 表达的影响。

• DOI: 10.1177/1535370215602785
• 发表时间: 2016
• 期刊: Experimental biology and medicine (Maywood, N.J.)
• 作者: Huang,Chun-Jung;Slusher,AaronL;Whitehurst,Michael;Wells,Marie;Maharaj,Arun;Shibata,Yoshimi
• 通讯作者: Shibata,Yoshimi

Exercise reduced pentraxin 3 levels produced by endotoxin-stimulated human peripheral blood mononuclear cells in obese individuals.

运动降低了肥胖个体内毒素刺激的人外周血单核细胞产生的五聚蛋白 3 水平。

• DOI: 10.1177/1535370217706963
• 发表时间: 2017
• 期刊: Experimental biology and medicine (Maywood, N.J.)
• 作者: Slusher,AaronL;Shibata,Yoshimi;Whitehurst,Michael;Maharaj,Arun;Quiles,JustinM;Huang,Chun-Jung
• 通讯作者: Huang,Chun-Jung