title: MicroRNA-487b Is a Negative Regulator of Macrophage Activation by Targeting IL-33 Production.
abstract: MicroRNAs (miRNAs) are short noncoding RNAs that regulate a broad spectrum of biological processes, including immune responses. Although the contributions of miRNAs to the function of immune cells are beginning to emerge, their specific roles remain largely unknown. IL-33 plays an important role in macrophage activation for innate host defense and proinflammatory responses. In this study, we report that miR-487b can suppress the levels of mRNA and protein for IL-33 during the differentiation of bone marrow-derived macrophages (BMDMs). This results in inhibition of IL-33-induced expression of Ag-presenting and costimulatory molecules and proinflammatory mediators. A luciferase assay showed that miR-487b binds to the IL-33 3'-untranslated region. We also confirmed that IL-33 directly promotes the activation of BMDMs by increasing the expression of MHC class I, MHC class II, CD80/CD86, and inducible NO synthase (iNOS) in a dose-dependent manner. Exposure of BMDMs to the TLR4 ligand, LPS, decreased miR-487b expression, increased IL-33 transcript levels, and induced the production of proinflammatory mediators (e.g., iNOS, IL-1β, IL-6, and TNF-α). Treatment with a specific inhibitor of miR-487b function also resulted in increased levels of IL-33 mRNA, which augmented LPS-induced expression of these inflammatory mediators in macrophages. Collectively, our results indicate that miR-487b plays a negative regulatory role in macrophages by controlling the levels of IL-33 transcript and protein to fine-tune innate immune host defense and proinflammatory responses of these cells. Thus, miR-487b plays an important role in the regulation of macrophage homeostasis and activation by targeting IL-33 transcripts.
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales 2038, Australia; Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, People's Republic of China; and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales 2038, Australia;
authors.forename: Fiona
authors.initials: F
authors.lastname: Eyers
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales 2038, Australia;
authors.forename: Hock L
authors.initials: HL
authors.lastname: Tay
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales 2038, Australia; Ming.Yang@newcastle.edu.au Paul.Foster@newcastle.edu.au.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales 2038, Australia; Ming.Yang@newcastle.edu.au Paul.Foster@newcastle.edu.au.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D001665:Binding Sites / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D000067596:Interleukin-33 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D020413:3' Untranslated Regions; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C587672:IL1B protein, mouse; C506535:Il33 protein, mouse; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D008070:Lipopolysaccharides; C000609796:MIRN487 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse