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Effects of Bacteria Expressing Invasin on Inflammatory Sequelae in a Colitis Model

机译：表达结肠炎细菌对结肠炎模型中炎症后遗症的影响

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摘要

The inflammatory bowel diseases, ulcerative colitis and Crohn's disease are common ailments in found in modern society. There is currently no medical cure for inflammatory bowel diseases, and treatment is given with the goal of remission of inflammatory bowel disease symptoms and improving patient quality of life. Surgical intervention is an option for patients in severe cases of inflammatory bowel disease, and may be curative for patients with ulcerative colitis but not for patients with Crohn's disease. Current treatment options available include 5-aminosalicylic acid drugs, corticosteroids, anti-tumor necrosis factor-? biologics, and antibiotics. To improve the efficacy of therapeutic options available to patients, it is necessary to develop novel treatments for inflammatory bowel diseases with reduced toxicity. When the inflammatory sequelae associated with inflammatory bowel diseases is left untreated, patients may experience significant morbidity and may become susceptible to developing colorectal cancer. Recent work with Yersinia enterocolitica has demonstrated the efficacy of using a bacterial treatment which expresses the adhesin invasin to activate the nod-like receptor family, pyrin domain-containing 3 inflammasome. This allows for expression of the immunomodulatory cytokine interleukin-18, which has shown to be protective against colitis and development of colitis associated colorectal cancer using a murine model. We propose that by administering an invasin expressing bacterial treatment to mice, the mice will demonstrate decreased inflammatory sequelae in colitis and colitis associated colorectal cancer models. This study compares the effects of dosing schemes and experimental treatment protocols using bacteria expressing invasin in a dextran sodium sulfate induced acute and chronic colitis models, and azoxymethane/dextran sodium sulfate induced colitis associated cancer models. Treatment with bacteria expressing invasin decreased morbidity and inflammatory sequelae in wildtype mice in acute colitis and colitis associated colorectal cancer models. Mice deficient in the nod-like receptor family, pyrin domain-containing 3 inflammasome also has decreased morbidity in acute colitis and colitis associated cancer models, regardless of treatment. Whereas, mice deficient in the interleukin 18 receptor had increased morbidity in acute and colitis associated colorectal cancer models. In a chronic colitis model, no differences were observed between dosing schemes of treatment with bacteria expressing invasin in wildtype mice. The results of this study will prove useful in further understanding the effects invasion expressing bacteria has on activation of the nod-like receptor family, pyrin domain-containing 3 inflammasome and the ability of interleukin-18 expression to be beneficial in the outcome of colitis and colorectal cancer models.
机译：炎症性肠病，溃疡性结肠炎和克罗恩氏病是现代社会常见的疾病。当前尚无用于治疗炎症性肠病的药物，并且以减轻炎症性肠病症状和改善患者生活质量为目标进行治疗。对于严重的炎症性肠病患者，手术干预是一种选择，对于溃疡性结肠炎患者可能是治愈的，但对克罗恩病患者则无效。当前可用的治疗选择包括5-氨基水杨酸药物，皮质类固醇，抗肿瘤坏死因子-β。生物制剂和抗生素。为了提高对患者可用的治疗选择的功效，有必要开发毒性降低的炎性肠疾病的新疗法。如果不治疗与炎症性肠病相关的炎症性后遗症，患者可能会出现明显的发病率，并且可能容易患上结直肠癌。最近与小肠结肠炎耶尔森氏菌的研究表明，使用表达黏附素侵袭素的细菌处理来激活nod样受体家族（含吡啶结构域的3个炎性体）的功效。这允许表达免疫调节细胞因子白细胞介素18，其已经显示出对鼠类结肠炎和结肠炎相关结肠直肠癌的保护作用。我们提出，通过对小鼠施用表达invasin的细菌治疗，小鼠将在结肠炎和结肠炎相关的大肠癌模型中显示出炎症后遗症减少。这项研究比较了使用表达葡聚糖的细菌在右旋糖酐硫酸钠诱发的急性和慢性结肠炎模型以及由甲氧甲烷/右旋糖酐硫酸钠诱发的结肠炎相关的癌症模型中给药方案和实验治疗方案的影响。在急性结肠炎和与结肠炎相关的大肠癌模型中，用表达invasin的细菌进行治疗可降低野生型小鼠的发病率和炎症后遗症。缺乏nod样受体家族的小鼠，含有吡喃结构域的3炎性小体，无论治疗如何，在急性结肠炎和结肠炎相关的癌症模型中的发病率也降低。然而，在急性和结肠炎相关的大肠癌模型中，缺乏白介素18受体的小鼠发病率增加。在慢性结肠炎模型中，在野生型小鼠中用表达入侵素的细菌治疗的给药方案之间没有观察到差异。这项研究的结果将有助于进一步理解侵袭表达细菌对nod样受体家族激活，含吡喃结构域的3个炎性小体的激活以及白介素18表达对结肠炎和结局的有益作用。大肠癌模型。

著录项

  • 作者

    Hassan, Elizabeth A.;

  • 作者单位

    The University of Texas Health Science Center at San Antonio.;

  • 授予单位 The University of Texas Health Science Center at San Antonio.;
  • 学科 Microbiology.;Immunology.
  • 学位 M.S.
  • 年度 2017
  • 页码 81 p.
  • 总页数 81
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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