title: MiR-146a modulates macrophage polarization in systemic juvenile idiopathic arthritis by targeting INHBA.
abstract: Monocytes from patients with systemic juvenile idiopathic arthritis (SJIA) have both features of classical activated M1 and alternatively activated M2 macrophages. An increasing number of studies have indicated that microRNAs (miRNAs) are critical regulators of monocyte polarization. Here, we focused on miR-146a expression in SJIA and investigated the function of miR-146a in monocyte polarization. We found that miR-146a expression was highly up-regulated in SJIA monocytes and correlated with the systemic features. miR-146a was expressed at a higher level in monocytes polarized with M2 conditions than those polarized with M1 conditions. miR-146a overexpression significantly decreased the production of M1 phenotype markers such as IL-6, IL-12, TNF-α, CD86 and iNOS in M1 macrophages, but increased the production of M2 marker genes such as Arg1, CCL17, CCL22 and CD206 in M2 macrophages. Conversely, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. We subsequently demonstrated that miR-146a targeted the 3'-untranslated region (UTR) of INHBA to inhibit its expression. Additionally, INHBA overexpression rescued the reduced IL-6, IL-12, and TNF-α levels induced by miR-146a overexpression in M1 macrophages, and rescued the increased Arg1, CCL17, and CCL22 levels induced by miR-146a overexpression in M2 macrophages. Similarly, the effects of miR-146a inhibition in monocyte polarization were all partly reversed by INHBA inhibition. Taken together, the data suggest that miR-146a serves as a molecular regulator in monocyte polarization and might play an important role in monocytes from patients with SJIA.
authors.affiliation: Department of Immunology and Rheumatology, Affiliated Children's Hospital of Xi'an Jiaotong University, 69 Xijuyuan Lane, Xi'an, Shaanxi Province 710003, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Pediatric Diseases, Affiliated Children's Hospital of Xi'an Jiaotong University, 69 Xijuyuan Lane, Xi'an, Shaanxi Province 710003, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Duan
authors.affiliation: Department of Immunology and Rheumatology, Affiliated Children's Hospital of Xi'an Jiaotong University, 69 Xijuyuan Lane, Xi'an, Shaanxi Province 710003, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Immunology and Rheumatology, Affiliated Children's Hospital of Xi'an Jiaotong University, 69 Xijuyuan Lane, Xi'an, Shaanxi Province 710003, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Geng
authors.affiliation: Department of Immunology and Rheumatology, Affiliated Children's Hospital of Xi'an Jiaotong University, 69 Xijuyuan Lane, Xi'an, Shaanxi Province 710003, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Fifth Road, Xi'an, Shaanxi Province 710004, China. Electronic address: wanggangzhangwgz@163.com.
authors.forename: Wanggang
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001171:Arthritis, Juvenile / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002648:Child; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits
keywords: INHBA; Macrophage polarization; MiRNA-146a; Systemic juvenile idiopathic arthritis