Post-Exposure JNJ-26366821 Treatment Attenuates Systemic Inflammation and Limits Cardiotoxic Risk

Figures

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  Figure 1. Experimental workflow of the research study showing the administration of the JNJ-26366821 drug 24 h after 8.0 Gy radiation exposure. A parallel cohort of naïve mice was euthanized as the baseline. The dashed arrows show the timeline and the red dots represent the time of euthanizing the mice and collecting heart and blood samples. The white dots represent the timepoints, when no euthanasia took place, but other procedures were conducted, such irradiation and drug administration. First round of euthanasia took place 2 h after drug administration.

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  Figure 2. Longitudinal profile of a selected panel of inflammatory proteins in JNJ-26366821 and saline-treated mice. All data were normalized to day 1 samples. (A) Pro-inflammatory molecules (IL-1a, IL-1b, IL-2, IL-3, IL-5, IL-6, IL-13, GM-CSF, IFN-gamma, KC, TNF-alpha, RANTES, IL-17a, and Eotaxin) (B) Anti-inflammatory molecules (IL-10 and G-CSF) and (C) molecules related to immune functions and pre both pro- and anti-inflammatory (IL-4, IL-9, MIP-1a, MCP, MIP-1b, IL-12p40, and IL-12p70).

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  Figure 3. PCA plots related to the untargeted omics assay. The sample legends are on the right-hand side. The saline- and JNJ-26366821-treated samples are depicted by circle and square, respectively. The timepoints are color graded. (A) Proteomics assay. The post-irradiated saline samples except 7 d-TSI are clustered together and encircled. Likewise, all post-irradiated JNJ-26366821 samples are clustered together and encircled. (B) Metabolomics assay. The saline and JNJ-26366821 samples were clustered together according to the time since irradiation. (C) Lipidomics assay. The naïve and post-irradiated samples were largely clustered together, except 7 d-TSI saline and 1 d-TSI JNJ-26366821 samples, respectively.

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  Figure 4. Functional network linked to cell death and cardiac health. The nodes are color coded based on their regulation status at one day (1 d) post-TBI. The edges connecting the nodes represent their relationship; arrow-headed: activated; blunt: association. The white nodes are not directly part of these networks but inserted as the intermediate between the network and TPO.