title: Cellular and urinary microRNA alterations in NZB/W mice with hydroxychloroquine or prednisone treatment.
abstract: 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 12 weeks beginning at 24 weeks-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.
authors.affiliation: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States. Electronic address: cchafin@vt.edu.
authors.forename: Cristen B
authors.initials: CB
authors.lastname: Chafin
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Regna
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hammond
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006886:Hydroxychloroquine / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000378:metabolism*; D011241:Prednisone / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D035683:MicroRNAs; D006886:Hydroxychloroquine; D011241:Prednisone
keywords: Hydroxychloroquine; MicroRNAs; NZB/W mice; Prednisone; Systemic lupus erythematosus