title: Aberrant T cell expression of Ca2+ influx-regulated miRNAs in patients with systemic lupus erythematosus promotes lupus pathogenesis.
abstract: OBJECTIVE
  The aim of this study was to investigate the pathogenic role of calcium (Ca(2+)) influx-regulated microRNAs (miRNAs) in T cells from patients with SLE.
  
  
  METHODS
  Expression profiles of 270 human miRNAs in Jurkat cells co-cultured with or without ionomycin were analysed by real-time PCR. Differential expression of miRNAs in T cell samples from 28 patients with SLE (SLE T cells) and 20 healthy controls were investigated using western blot analysis of proteins expressed by respective miRNA target transcripts. Transfection studies were conducted to investigate miRNA-specific biological functions.
  
  
  RESULTS
  Initial analysis revealed differential expression of nine miRNAs in Jurkat cells after co-culture with ionomycin. Of these, miR-524-5p and miR-449b were overexpressed in SLE T cells. Levels of expressed miR-524-5p showed a significant direct correlation with the SLEDAI. Transfection of Jurkat cells with miR-524-5p mimic suppressed Jagged-1 and Hes-1 protein expression. Likewise, expression of both Jagged-1 and Hes-1 proteins were diminished in SLE T cells. Upon activation of Jurkat cells transfected with miR-524-5p mimic, production of IFN-γ increased but the apoptotic rate was unaffected.
  
  
  CONCLUSIONS
  In SLE T cells, miR-524-5p and miR-449b (both regulated by Ca(2+) influx) were overexpressed. Moreover, increased miR-524-5p expression, as shown by patients with SLE, directly paralleled disease activity (SLEDAI). Transfection of miR-524-5p also enhanced IFN-γ production in activated Jurkat cells.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Lu
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Yu
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Yu
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
authors.forename: Hsien-Bin
authors.initials: HB
authors.lastname: Huang
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, School of Medicine, Tzu Chi University, Hualien, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Department of Biomedical Sciences, Chang Gung University, Taoyuan and Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. tzuchilai@gmail.com.
authors.forename: Ning-Sheng
authors.initials: NS
authors.lastname: Lai
mesh_terms: D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D000072100:Jagged-1 Protein; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D013601:T-Lymphocytes / Q000378:metabolism*; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002118:Calcium; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D035683:MicroRNAs; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C000606273:JAG1 protein, human; C078493:HES1 protein, human
keywords: Ca2+ influx; Notch; T cells; miR-449b; miR-524-5p; systemic lupus erythematosus