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Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients

ABSTRACT: Purpose: We analyzed RNA-seq from peripheral blood mononuclear cells (PBMC) in DMARDs-naïve RA patients and healthy subjects. Our goal was to evaluate the transcriptional profiles of ST2825-treated PBMC to identify its therapeutic potential. Methods: We analyzed bulk RNA-seq from peripheral blood mononuclear cells (PBMC) in DMARDs-naïve RA patients after stimulation with LPS and IL-1β, PBMC were treated with the MyD88 chemical inhibitor, ST2825. Collection of RNA was performed after 24 h of treatment and samples were sequenced to determine transcriptional changes and regulated processes in treated PBMC. Results: paired-end reads were mapped to the hg19 human genome assembly. RNA levels were normalized using DESeq. We identified 796 differentially expressed (DE) genes by 2-fold change (p<0.05) between RA patients and healthy subjects. Our analysis revealed 631 DE genes between DMARDs-naïve RA patients before and after ST2825 treatment. We identified 471 DE genes between LPS-stimulated RA PBMC and LPS-stimulated RA PBMC treated with ST2825. Conclusion: Our study provides comprehensive evidence supporting the potential application of the MyD88 inhibitor, ST2825, as a modulator of gene expression signtaures involved in pathogenic processes in PBMC from DMARDs-naïve RA patients. Our indepth analysis of RNA-seq data will serve as a valuable resource containing the inflammatory gene expression signatures by MyD88.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189136 | GEO | 2021/11/30

REPOSITORIES: GEO

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Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients

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8cabb52f-f5ec-4f58-8bff-c3c8a2140d47 - samples

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