hes1-protein--human and Lupus-Erythematosus--Systemic

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.. 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.. 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.. 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.

Topics: Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Calcium; Calcium-Binding Proteins; Homeodomain Proteins; Humans; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Jagged-1 Protein; Jurkat Cells; Lupus Erythematosus, Systemic; Membrane Proteins; MicroRNAs; Serrate-Jagged Proteins; T-Lymphocytes; Transcription Factor HES-1