# Modulation of chemokine signaling to mitigate radiation induced inflammation

> **NIH NIH U01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $671,909

## Abstract

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.

## Key facts

- **NIH application ID:** 10844534
- **Project number:** 5U01AI170036-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Richard J DiPaolo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,909
- **Award type:** 5
- **Project period:** 2022-07-21 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844534

## Citation

> US National Institutes of Health, RePORTER application 10844534, Modulation of chemokine signaling to mitigate radiation induced inflammation (5U01AI170036-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10844534. Licensed CC0.

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