EPITHELIAL-LYMPHOID CROSSTALK VIA IL-1, DEFENSE AGAINST CITROBACTER RODENTIUM

通过 IL-1 进行上皮-淋巴串扰，防御啮齿类柠檬酸杆菌

• 批准号: 8167833
• 负责人: JISHU SHI
• 金额: $ 21.84万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167833
• 关键词: Adhesions; Bacterial Proteins; Cell Proliferation; Cells; Citrobacter rodentium; Clinical; Colon; Computer Retrieval of Information on Scientific Projects Database; Epithelial; Epithelial Cell Proliferation; Epithelial Cells; Funding; Gap Junctions; Grant; HT29 Cells; Homeostasis; Host Defense; Hyperplasia; Immune; Immunoglobulins; Infection; Inflammatory; Institution; Interleukin-1; Interleukin-1 Receptors; Interleukin-18; Intestines; Killer Cells; Liver; Lymphoid; Mucosal Immunity; Mus; Natural Immunity; Neutrophil Infiltration; Production; Proteins; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Spleen; Tight Junctions; United States National Institutes of Health; antimicrobial peptide; cytokine; macrophage; migration; protein expression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this proposal is to determine the role of IL-1 receptor type I (IL-1R1) in host defense against Citrobacter rodentium infection. We hypothesize that IL-1R1-initiated signaling is essential for MyD88-dependent mucosal immunity against Citrobacter rodentium. Specific Aim One: Determine the role of IL-1R1 signaling in intestinal epithelial cell homeostasis in C. rodentium infection. We hypothesize that IL-1R signaling is essential for intestinal epithelial cell proliferation, functional integrity, and antimicrobial peptide/protein expression in C. rodentium infection. Using HT-29 and Mode-K cells, we will determine the effects of IL-1¿ on cell proliferation, migration, and adhesion, as well as the expression of antimicrobial peptides and proteins, proinflammatory cytokine, and molecules involved in gap junction and tight junction. In addition, we will compared the clinical signs, colonic hyperplasia, and intestinal mucosal integrity in WT, MyD88 KO, IL-1R1 KO, and IL-18 KO mice infected with C. rodentium. Specific Aim Two: Determine the role of IL-1R signaling in mucosal innate immunity in C. rodentium infection. We hypothesize that IL-1R signaling is required for the induction and recruitment of neutrophils and the production of inflammatory cytokines by epithelial and immune cells in C. rodentium infection. We will evaluate the colonic production of proinflammatory cytokines, intestinal infiltration of neutrophils and macrophages, epithelial antimicrobial peptides and proteins, bacterial burden in segments of colon, liver, and spleen, and intestinal immunoglobulin levels on WT, MyD88 KO, IL-1R1 KO, and IL-18 KO mice infected with C. rodentium.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是确定IL-1受体I型（IL-1 R1）在宿主防御啮齿类柠檬酸杆菌感染中的作用。我们假设IL-1 R1启动的信号传导对于MyD 88依赖的针对啮齿类柠檬酸杆菌的粘膜免疫是必不可少的。 具体目的一：确定IL-1 R1信号在肠上皮细胞稳态中的作用。啮齿类感染 我们假设IL-1 R信号传导对于肠上皮细胞增殖、功能完整性和C.啮齿类感染 使用HT-29和Mode-K细胞，我们将确定IL-1？对细胞增殖、迁移和粘附的影响，以及抗菌肽和蛋白质、促炎细胞因子和参与间隙连接和紧密连接的分子的表达。 此外，我们将比较感染C的WT、MyD 88 KO、IL-1 R1 KO和IL-18 KO小鼠的临床体征、结肠增生和肠粘膜完整性。啮齿动物。 具体目的二：确定IL-1 R信号在C.啮齿类感染 我们推测，IL-1 R信号传导是诱导和募集中性粒细胞以及上皮细胞和免疫细胞产生炎性细胞因子所必需的。啮齿类感染我们将评估感染C.的WT、MyD 88 KO、IL-1 R1 KO和IL-18 KO小鼠的促炎细胞因子的结肠产生、中性粒细胞和巨噬细胞的肠浸润、上皮抗微生物肽和蛋白、结肠、肝脏和脾脏节段中的细菌负荷以及肠免疫球蛋白水平。啮齿动物。