Inflammasome regulation underlying sexual dimorphism in periodontitis

牙周炎性别二态性背后的炎症小体调节

基本信息

批准号：
10639301
负责人：
Julie Teresa Marchesan
金额：
$ 71.92万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10639301
关键词：
Adjuvant Therapy Adult Alveolar Bone Loss American Biological Biological Process Bone Diseases CASP1 gene Caring Cell Death Cell membrane Chronic Disease Data Data Analyses Development Disease Excision Female Fostering Gene Deletion Genetic Gingiva Gingivitis Goals Health Health Personnel High Prevalence Homeostasis IL18 gene Immune response Individual Inflammasome Inflammation Inflammation Mediators Inflammatory Innate Immune System Interleukin-1 Interleukin-1 beta Interleukins Knowledge Ligature Modeling Mucous Membrane Mus Ovariectomy Pathway interactions Patients Pattern recognition receptor Peptide Hydrolases Periodontal Diseases Periodontitis Periodontium Population Prevalence Prevention Process Production Quality of life Regulation Resolution Role Severities Severity of illness Sex Differences Signal Transduction Testing Therapeutic Tissues Tooth Loss Tooth structure Woman biological sex bone bone loss bone repair cell type cohort comparative efficacy cytokine healing human tissue immune cell infiltrate innate immune function male men microbial mortality novel prevent protein complex repaired response sensor sex sexual dimorphism standard of care therapeutic target tissue repair translational applications treatment response

项目摘要

ABSTRACT Periodontitis is a male-dominant, heterogeneous, inflammatory disease of the bone and tissues supporting the tooth. It is one of the most prevalent non-communicable chronic diseases, with ~50% prevalence in the American population. Currently, there are no adjuvant therapies available to treat the 20-25% of “hyper-inflammatory” patients that progress to tooth loss despite appropriate standard of care. In support of this current proposal, inflammasome modulation has been proposed to treat several inflammatory diseases. Inflammasome is required for processing of pro-interleukin (IL)-1, pro-IL-18, and Gasdermin-D into their mature, functional forms. Despite the common knowledge that IL-1 is sexually dimorphic and a marker for periodontal inflammation, its role as a direct driver of disease development in both females and males is not clear. We find that inflammasome activation has both a protective and destructive effect on periodontal tissue that is differentially regulated between the sexes. Our data suggest the existence of sex-based distinct pathways of periodontal bone loss. This study will expand our current knowledge on the role of inflammasomes in periodontal inflammation and tissue destruction in females and males. We propose to build upon our findings to develop the below aims: Aim 1: Define the impact of biological sex in inflammasome activation during periodontal disease development and progression. Aim 2: Define the relationship between inflammasomes and periodontal tissue repair. Aim 3: To use a new strategy to target inflammasomes for preventing murine periodontitis. 1

抽象的牙周炎是一种男性占主导地位的异质性骨和组织炎症性疾病它是最常见的非传染性慢性疾病之一。目前，美国人群中的患病率约为 50%，尚无可用的辅助疗法。治疗 20-25% 的“高炎症”患者，尽管为了支持当前的提议，炎性体调节已被采用。已提出治疗多种炎症性疾病需要炎性体进行处理。将白介素原 (IL)-1、IL-18 原和 Gasdermin-D 转化为成熟的功能形式。众所周知，IL-1 具有性别二态性，是牙周病的标志物炎症，其作为女性和男性疾病发展的直接驱动因素的作用并不我们发现炎症小体的激活既具有保护作用，又具有破坏作用。我们的数据表明，不同性别的牙周组织受到不同的调节。存在基于性别的不同牙周骨质流失途径。这项研究将扩大我们的研究范围。关于炎症小体在牙周炎症和组织中的作用的最新知识我们建议根据我们的发现制定以下内容。目标：目标 1：定义生物性别对牙周炎症小体激活的影响目标 2：确定炎症小体之间的关系。目标 3：使用一种新策略来靶向炎症小体。预防小鼠牙周炎。 1