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Negative regulation of inflammation during Klebsiella pneumoniae infection

肺炎克雷伯菌感染期间炎症的负调节

基本信息

批准号：
10301091
负责人：
Giraldina Trevejo-Nunez
金额：
$ 23.48万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-11 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10301091
关键词：
3&apos Untranslated Regions ATAC-seq Affect Animal Model Animals Biological Response Modifiers Cell Line Chromatin Code Complement Data Epigenetic Process Epithelial Epithelial Cells Event Gene Expression Genes Genetic Transcription Histone Deacetylase Histones Human Immune response Immunity Immunocompromised Host In Vitro Infection Inflammation Inflammatory Interleukin-17 Klebsiella pneumoniae Lung Mediating Medical Messenger RNA Microbe Morbidity - disease rate Multi-Drug Resistance Nosocomial pneumonia Pneumonia Process RNA-Binding Proteins Receptor Signaling Regulation Resistance Resistance profile Role Signal Pathway Signal Transduction Tissues Transcript Transcriptional Regulation United States airway epithelium base bronchial epithelium chromatin remodeling conditional knockout cytokine fight against human RNA sequencing improved mortality mouse model pathogen receptor resistance gene respiratory

项目摘要

Project Summary Infections with Klebsiella pneumoniae (KP) activate the IL-17 signaling pathway, which is crucial to constrain KP dissemination and facilitate pathogen eradication. During this process, IL-17 is negatively regulated by RNA binding proteins (RBP) in an effort to decrease collateral tissue damage in the host. One of these RBPs is Regnase-1 (Reg1) which degrades IL-17- induced transcripts either through the coding region or 3'UTR. In this proposal, we will investigate the role of Reg1 in the airway epithelium during KP pneumonia. We hypothesize that Reg1 deficiency enhances the effect of pro-inflammatory transcripts in the airway epithelium which favors immunity against KP. For that purpose, we will characterize a Reg1 conditional knockout in the airway epithelium upon KP pneumonia as well as investigate Reg1 regulation at the epigenetic and post-transcriptional level.

项目摘要肺炎克雷伯氏菌（KP）感染激活IL-17信号通路，这对抑制KP至关重要传播和促进病原体根除。在此过程中，IL-17受RNA负调控，结合蛋白（RBP），以减少宿主的附带组织损伤。这些限制性商业惯例之一是 Regnase-1（Reg 1），通过编码区或3 'UTR降解IL-17诱导的转录物。在这建议，我们将调查的作用，Reg 1在气道上皮在KP肺炎。我们假设 Reg 1缺陷增强了气道上皮中促炎转录物的作用，对KP的豁免权。为此，我们将描述气道上皮中Reg 1条件性敲除的特征，以及研究Reg 1在表观遗传和转录后水平的调控。