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Triterpenoids in mitigation of radiation induced acute or delayed inflammation

三萜类化合物可减轻辐射引起的急性或迟发性炎症

基本信息

批准号：
10852214
负责人：
Richard J DiPaolo
金额：
$ 13.42万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-21 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10852214
关键词：
Acids Acute Address Aftercare Agonist Anti-Inflammatory Agents Antineoplastic Agents Antioxidants Bone Marrow CCL2 gene CCR Cell Culture Techniques Cell Proliferation Cells Chemical Injury Chemicals Chest Circulation Clinical Trials Collaborations Data Development Dose Esters Exposure to Eye Injuries Fibrosis Funding Gastrointestinal tract structure Gene Deletion Genes Grant Hour Immune Inflammation Inflammation Mediators Inflammatory Injury Laboratories Licensure Ligands Lung Modeling Mucous Membrane Multiple Organ Failure Mus Myelogenous Myeloid Cells NQO1 gene National Institute of Allergy and Infectious Disease Nuclear Nuclear Accidents Oleanolic Acid Organ Oxidative Stress Oxidative Stress Induction Parents Pathway interactions Play Population Production Publishing Pulmonary Fibrosis Pulmonary Inflammation Radiation Radiation Accidents Radiation Injuries Radiation Syndromes Radiation Toxicity Radiation exposure Radiation induced damage Radio Rationalization Reporting Research Resistance Risk Role Schedule Signal Transduction Site Syndrome T-Lymphocyte Terpenes Terrorism Testing Tissues Toxic effect Validation Work animal rule chemical countermeasure chemokine chemokine receptor efficacy study epithelial injury gastrointestinal heme oxygenase-1 injured irradiation jejunum mass casualty medical countermeasure monocyte mouse model nuclear factor-erythroid 2 oleanane pre-clinical programs radiation mitigation radiation resistance radioresistant recruit systemic inflammatory response tissue injury

项目摘要

Project Summary Currently, there is a need for strategies that mitigate acute and delayed radiation syndrome. The risk of large populations encountering radiation exposure is real and growing. Radiation induced inflammation plays significant role in inducing radiation toxicity. Chemokine signaling plays key role in systemic and local inflammation by modulating egress and recruitment inflammatory immune cells such as inflammatory monocytes and T cells. Radiation exposure induces recruitment of inflammatory cells and promotes systemic and local inflammation. We have observed that deletion of genes expressing chemokine receptor 2 in mice promotes resistance radiation induced acute and delayed inflammation. Triterprenoids are very potent anti-inflammatory agents. Recent findings suggest that synthetic derivatives of oleanolic acid that are more potent at suppressing production of the inflammatory mediator such as chemokine ligand 2. Under NIAID Chemical Countermeasures Research Program (CCRP) Triterprenoids such as CDDO- methyl ester (CDDO-Me) has been shown to mitigate chemical induced ocular injury by nrf2 dependent manner. In this proposal we will examine the effect of CDDO- Me against radiation induced acute and delayed inflammation using mice model of radiation induced gastrointestinal syndrome and radiation induced pulmonary syndrome respectively. We will also characterize the effect of CDDO-Me in modulation of bone marrow derived inflammatory immune cell recruitment in injured tissue. Determination of mechanism of action of will facilitate CDDO-Me as a medical countermeasure against radiation under the FDA’s Animal Rule.

项目总结