# JNJ-26366821 Attenuates Radiation-Induced Pro-Inflammatory Cytokines and miRNAs and Triggers TR/RXR Signaling Pathway

## TL;DR

A new drug reduces harmful inflammation and protects platelet counts in mice exposed to high radiation doses.

## Contribution

JNJ-26366821 reduces radiation-induced pro-inflammatory cytokines and miRNAs while activating TR/RXR signaling.

## Key findings

- TPOm pre-treatment reduces expression of pro-inflammatory cytokines after high-dose radiation.
- TPOm modulates miRNA expression in the spleen of irradiated mice at early and late time points.
- TPOm may protect against radiation-induced thrombocytopenia and lethality.

## Abstract

JNJ-26366821, a novel thrombopoietin mimetic peptide (TPOm), is shown to increase platelets (PLTs) transiently in peripheral blood. We hypothesized that increases in PLT counts may involve stimulation of hematopoiesis via induction of cytokines, growth factors, and microRNAs. Hence, we measured various cytokines, chemokines, and growth factors in serum. Time-course analysis of G-CSF, IL-5, IL-6, IL-9, IL-10, TNFα, IL-1α, and IL-1β expression was significantly altered in the control group at 9.5 Gy compared to a lower non-lethal dose of 7 Gy on days 7 to 15 post-exposure. TPOm pre-treatment significantly ameliorated the changes in expression of these pro-inflammatory cytokines and growth factors. Additionally, we show that TPOm differentially modulates the miRNA expression profiles in the spleen of irradiated mice compared to controls at both early times as well as later times after irradiation. These results suggest a possible role of TPOm in protecting animals from radiation-induced thrombocytopenia and lethality by attenuating radiation-induced inflammatory cytokines and miRNAs.