Inflammation

Gene expression

Systemic lupus erythematosus

Gene

Disease

Biology

Internal medicine

Immunology

Medicine

Chemokine

Proinflammatory cytokine

Flow cytometry

EZH2

Cancer research

Biochemistry

Arthritis & Rheumatology

Objective We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus‐like disease in MRL/ lpr mice. Methods EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL/ lpr mice was achieved by intraperitoneal 3′‐deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti–double‐stranded DNA (anti‐dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed. Results EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/ lpr mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in spl...

Inhibition of EZH2 Ameliorates Lupus‐Like Disease in MRL/<i>lpr</i> Mice

Inhibition of EZH2 Ameliorates Lupus‐Like Disease in MRL/lpr Mice