Control of Neutrophilic Inflammation in Intestinal Health and Disease

控制肠道健康和疾病中的中性粒细胞炎症

基本信息

项目摘要

Summary: The main objective of this proposal is to understand how neutrophils migrate across the intestinal epithelia, toward the eventual goal of manipulating this process in pathologic conditions where it can become excessive as in the context of idiopathic inflammatory intestinal disease as well as enteric bacterial infection. In particular, occurrence and severity of colitis appears to be correlated with the extent of neutrophil transmigration across the colonic epithelium and recent studies have shown that neutrophil migration can incite the migration of other cells that mediate inflammation. Thus, neutrophil transepithelial migration and accumulation at mucosal surfaces is a hallmark of many inflammatory conditions, and this process correlates directly with clinical disease activity and epithelial injury. Currently, the mechanisms that define neutrophil-epithelial interactions during an inflammatory response are not completely understood. To fill this gap in knowledge, we have uniquely shown that secretion of the eicosanoid hepoxilin A3 (HxA3) through the apically expressed efflux pump known as MRP-2 establishes the chemotactic gradient across the intestinal epithelium that is required for neutrophils from the submucosal space to move into the colonic lumen at times of inflammation. Additionally, we identified the N-acyl ethanolamine (NAE) class of eCBs to function in suppressing neutrophil transepithelial migration, and that these molecules are secreted through the apical efflux pump known as P-glycoprotein (P-gp). We hypothesize that these pro- and anti-inflammatory pathways communicate to provide a responsive, integrated mechanism to control inflammation status and that these are dysregulated in disease settings. To test this central hypothesis, we aim to identify the HxA3 receptor(s) on the cell surface of neutrophils (Aim 1), determine the nature of NAE-type ECBs/P-gp and HxA3/MRP2 signaling (Aim 2), and to explore crosstalk points between these two pathways that drive the inflammatory function of neutrophils (Aim 3). Successful completion of these Aims will provide a consolidated picture of mechanisms controlling neutrophil transmigration across the intestinal epithelium that will lead to both novel biological principles and therapeutic intervention strategies.
简介:

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Beth A McCormick其他文献

Beth A McCormick的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Beth A McCormick', 18)}}的其他基金

Intestinal Homeostasis Induced by Commensals
共生体诱导的肠道稳态
  • 批准号:
    10029718
  • 财政年份:
    2020
  • 资助金额:
    $ 59.58万
  • 项目类别:
Intestinal Homeostasis Induced by Commensals
共生体诱导的肠道稳态
  • 批准号:
    10611932
  • 财政年份:
    2020
  • 资助金额:
    $ 59.58万
  • 项目类别:
Intestinal Homeostasis Induced by Commensals
共生体诱导的肠道稳态
  • 批准号:
    10393697
  • 财政年份:
    2020
  • 资助金额:
    $ 59.58万
  • 项目类别:
Intestinal Homeostasis Induced by Commensals
共生体诱导的肠道稳态
  • 批准号:
    10212384
  • 财政年份:
    2020
  • 资助金额:
    $ 59.58万
  • 项目类别:
Bacterial regulation of lipid immuno-modulators in patients with ulcerative colitis
溃疡性结肠炎患者脂质免疫调节剂的细菌调节
  • 批准号:
    9374370
  • 财政年份:
    2017
  • 资助金额:
    $ 59.58万
  • 项目类别:
Control of Neutrophilic Inflammation in Intestinal Health and Disease
控制肠道健康和疾病中的中性粒细胞炎症
  • 批准号:
    10454910
  • 财政年份:
    2016
  • 资助金额:
    $ 59.58万
  • 项目类别:
Control of Neutrophilic Inflammation in Intestinal Health and Disease
控制肠道健康和疾病中的中性粒细胞炎症
  • 批准号:
    10263264
  • 财政年份:
    2016
  • 资助金额:
    $ 59.58万
  • 项目类别:
Intestinal Inflammation Orchestrated by Pathogens
由病原体精心策划的肠道炎症
  • 批准号:
    9147569
  • 财政年份:
    2015
  • 资助金额:
    $ 59.58万
  • 项目类别:
Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3
沙门氏菌发病机制和 Caspase-3 对分泌效应子的处理
  • 批准号:
    8705749
  • 财政年份:
    2013
  • 资助金额:
    $ 59.58万
  • 项目类别:
Molecular Mechanisms of the Inflammatory Response Induced by Shigella flexneri
福氏志贺菌引起炎症反应的分子机制
  • 批准号:
    8112166
  • 财政年份:
    2010
  • 资助金额:
    $ 59.58万
  • 项目类别:

相似海外基金

ATP Binding Cassette Transporters in Health and Disease
健康和疾病中的 ATP 结合盒转运蛋白
  • 批准号:
    10390366
  • 财政年份:
    2021
  • 资助金额:
    $ 59.58万
  • 项目类别:
ATP Binding Cassette Transporters in Health and Disease
健康和疾病中的 ATP 结合盒转运蛋白
  • 批准号:
    10237095
  • 财政年份:
    2021
  • 资助金额:
    $ 59.58万
  • 项目类别:
ATP Binding Cassette Transporters in Health and Disease
健康和疾病中的 ATP 结合盒转运蛋白
  • 批准号:
    10552563
  • 财政年份:
    2021
  • 资助金额:
    $ 59.58万
  • 项目类别:
Photosensitizing Nanoconstructs for Regulation of ATP-Binding Cassette Transporters in the Brain
用于调节大脑中 ATP 结合盒转运蛋白的光敏纳米结构
  • 批准号:
    2030253
  • 财政年份:
    2020
  • 资助金额:
    $ 59.58万
  • 项目类别:
    Standard Grant
Structural and functional studies of iron uptake ATP-binding cassette transporters (ABC transporters) in Gram-negative bacteria
革兰氏阴性菌中铁摄取 ATP 结合盒转运蛋白(ABC 转运蛋白)的结构和功能研究
  • 批准号:
    20K22561
  • 财政年份:
    2020
  • 资助金额:
    $ 59.58万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Investigating the mechanism of polysaccharide recognition and export by bacterial ATP-binding cassette transporters
研究细菌 ATP 结合盒转运蛋白识别和输出多糖的机制
  • 批准号:
    489384-2016
  • 财政年份:
    2018
  • 资助金额:
    $ 59.58万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Investigating the mechanism of polysaccharide recognition and export by bacterial ATP-binding cassette transporters
研究细菌 ATP 结合盒转运蛋白识别和输出多糖的机制
  • 批准号:
    489384-2016
  • 财政年份:
    2017
  • 资助金额:
    $ 59.58万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Investigating the mechanism of polysaccharide recognition and export by bacterial ATP-binding cassette transporters
研究细菌 ATP 结合盒转运蛋白识别和输出多糖的机制
  • 批准号:
    489384-2016
  • 财政年份:
    2016
  • 资助金额:
    $ 59.58万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
The Mechanism of ATP Binding Cassette Transporters
ATP 结合盒转运蛋白的机制
  • 批准号:
    318360
  • 财政年份:
    2014
  • 资助金额:
    $ 59.58万
  • 项目类别:
    Fellowship Programs
Heat shock protein 27 attenuates foam cell formation by enhancing cholesterol efflux via the ATP-binding cassette transporters A1
热休克蛋白 27 通过 ATP 结合盒转运蛋白 A1 增强胆固醇流出,从而减弱泡沫细胞形成
  • 批准号:
    304334
  • 财政年份:
    2014
  • 资助金额:
    $ 59.58万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了