Cellular and urinary microRNA alterations in NZB/W mice with hydroxychloroquine or prednisone treatment

Determining alterations to disease-associated miRNAs induced by specific therapeutics may allow the use of tailored therapy in lupus. We determined miRNA alterations in female NZB/W lupus mice treated with hydroxychloroquine (HCQ) or prednisone (PRED) for 12weeks beginning at 24weeks-of-age. B cell, PBMC, and urinary miR-let-7a expression were decreased with HCQ or PRED treatment. HCQ or PRED treatment reduced miR-21 expression in mesangial cells, T cells, pDCs, PBMCs, and the urine. MiR-146a expression was reduced in mesangial cells with HCQ treatment and in pDCs with HCQ or PRED treatment. PRED treatment increased miR-155 expression in mesangial, B, and T cells and PBMCs yet decreased miR-155 expression in pDCs and the urine. In vitro studies confirmed that HCQ or PRED's anti-inflammatory actions are dependent on their ability to inhibit miRNA expression. Our studies indicate that lupus therapeutics may work, in part, by altering the expression of disease-associated miRNAs. •We measured miRNA alterations in NZB/W mice treated with HCQ or PRED.•MiRNAs were measured in mesangial cells, splenocytes, PBMCs, and the urine.•HCQ or PRED differentially altered miRNA expression in cells and tissues.•MiRNA inhibition decreased HCQ or PRED's anti-inflammatory abilities in vitro.•Individualized therapy may be utilized based on miRNA expression.