PMID- 26936882 OWN - NLM STAT- MEDLINE DCOM- 20160816 LR - 20220129 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 196 IP - 8 DP - 2016 Apr 15 TI - MicroRNA-487b Is a Negative Regulator of Macrophage Activation by Targeting IL-33 Production. PG - 3421-8 LID - 10.4049/jimmunol.1502081 [doi] AB - 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-1beta, IL-6, and TNF-alpha). 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. CI - Copyright (c) 2016 by The American Association of Immunologists, Inc. FAU - Xiang, Yang AU - Xiang Y AD - 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. FAU - Eyers, Fiona AU - Eyers F AD - 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; FAU - Herbert, Cristan AU - Herbert C AD - Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia. FAU - Tay, Hock L AU - Tay HL AD - 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; FAU - Foster, Paul S AU - Foster PS AD - 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. FAU - Yang, Ming AU - Yang M AD - 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. LA - eng GR - MR/K006584/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160302 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (3' Untranslated Regions) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (Cd86 protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (IL1B protein, mouse) RN - 0 (Il33 protein, mouse) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-33) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (MIRN487 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) SB - IM MH - 3' Untranslated Regions/genetics MH - Animals MH - B7-1 Antigen/biosynthesis MH - B7-2 Antigen/biosynthesis MH - Binding Sites/genetics MH - Bone Marrow Cells/cytology/immunology MH - Cell Differentiation/immunology MH - Cells, Cultured MH - DNA-Binding Proteins/genetics/immunology MH - Histocompatibility Antigens Class I/biosynthesis MH - Histocompatibility Antigens Class II/biosynthesis MH - Interleukin-1beta/biosynthesis MH - Interleukin-33/*biosynthesis/genetics/immunology MH - Interleukin-6/biosynthesis MH - Lipopolysaccharides MH - Macrophage Activation/genetics/*immunology MH - Macrophages/*immunology MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/antagonists & inhibitors/biosynthesis/*genetics MH - Nitric Oxide Synthase Type II/biosynthesis MH - RNA, Messenger/genetics MH - Tumor Necrosis Factor-alpha/biosynthesis EDAT- 2016/03/05 06:00 MHDA- 2016/08/17 06:00 CRDT- 2016/03/04 06:00 PHST- 2015/09/22 00:00 [received] PHST- 2016/02/03 00:00 [accepted] PHST- 2016/03/04 06:00 [entrez] PHST- 2016/03/05 06:00 [pubmed] PHST- 2016/08/17 06:00 [medline] AID - jimmunol.1502081 [pii] AID - 10.4049/jimmunol.1502081 [doi] PST - ppublish SO - J Immunol. 2016 Apr 15;196(8):3421-8. doi: 10.4049/jimmunol.1502081. Epub 2016 Mar 2.