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Modulation of chemokine signaling to mitigate radiation induced inflammation

调节趋化因子信号传导以减轻辐射引起的炎症

基本信息

批准号：
10474889
负责人：
Richard J DiPaolo
金额：
$ 71.98万
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/10474889
关键词：
Acute Affect Aftercare Animals Anti-Inflammatory Agents Antineoplastic Agents Atherosclerosis B-Lymphocytes Basophils Blood Circulation Bone Marrow Bone Marrow Involvement Cell Lineage Cells Data Development Disease Dose Early treatment Exposure to Extramedullary FOXP3 gene Face Gene Deletion Hematopoietic Hour Human Immune Immune response Inflammation Inflammatory Inflammatory Response Injury Intestines Knockout Mice Licensure Lung Lymphocyte Modeling Multiple Organ Failure Mus Myelogenous Myeloid Cells Nuclear Nuclear Accidents Peritoneal Macrophages Pharmacology Play Population Pulmonary Fibrosis Radiation Radiation Accidents Radiation Injuries Radiation Syndromes Radiation Toxicity Radiation exposure Regulatory T-Lymphocyte Research Resistance Rheumatoid Arthritis Risk Role Schedule Signal Transduction Site Structure of parenchyma of lung Surface Syndrome T memory cell T-Lymphocyte Terrorism Testing Therapeutic Time Tissues Toxic effect Whole-Body Irradiation aged animal rule antagonist base chemokine chemokine receptor effector T cell experimental study gastrointestinal in vivo inhibitor inhibitor therapy injured intestinal injury irradiation mass casualty medical countermeasure monocyte mouse model multiorgan damage radiation effect radiation mitigation radiation resistance radioresistant recruit repair function therapeutic evaluation therapeutic target tissue repair trafficking

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 radiation resistance. Pharmacological inhibition of CCR2 signaling mitigates acute radiation syndrome in mice. Moreover these animals receiving CCR2 antagonist treatment did not develop delayed effect of acute radiation exposure (DEARE) such as radiation induced pulmonary syndrome. In this proposal we will examine the effect of CCR2 inhibitor against radiation induced acute and delayed inflammation using mice model of acute and delayed radiation injury. We will fully characterize CCR2 antagonist treatment with a determination of an optimum dose and schedule for mitigation of radiation induced acute and delayed inflammation. We will examine the general applicability of this strategy in young and aged animals. We will also characterize the effect of CCR2 antagonist in in modulation of bone marrow derived inflammatory immune cell release and recruitment in injured tissue. Determination of mechanism of action of will facilitate CCR2 inhibitor as a medical countermeasure against radiation under the FDA’s Animal Rule.

项目总结