Just Jesper, Munk Ipsen Pernille, Kruhøffer Mogens, Lykkemark Simon, Skjold Tina, Schiøtz Peter Oluf, Hoffmann Hans Jürgen
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
Int Arch Allergy Immunol. 2019;179(2):102-107. doi: 10.1159/000496513. Epub 2019 Apr 9.
MicroRNAs (miRNAs) represent important post-transcriptional regulators with a dynamic expression profile during health and disease.
We explored the miRNA profile of human mast cells (MCs) during sen-sitization with IgE, during activation through IgE, and relat ed it to prostaglandin D2 synthesis and histamine release.
We investigated the expression pattern of 762 miRNAs during the IgE-mediated sensitization and activation of MCs cultured from CD133+ stem cells that were isolated from allergic asthmatic patients and nonatopic controls.
IgE-mediated sensitization increased the expression of miRNA-210 eight-fold. This increase was sustained during IgE-mediated MC activation. Furthermore, we confirmed the increase of the miRNA-132/212 cluster after MC activation. Predicted target genes of miRNA-210/132/212 were enriched in several pathways known to be involved in MC activation. Histamine release was significantly higher in MCs from allergic patients when compared to controls, and a number of miRNAs correlated with histamine release and prostaglandin D2 synthesis during MC activation.
The miRNAs and analysis presented here can help to elucidate the role of miRNAs in mediator release during MC activation. We speculate that miRNA-210 could be important in MC sensitization that leads to allergic symptoms.
微小RNA(miRNA)是重要的转录后调节因子,在健康和疾病状态下具有动态表达谱。
我们探究了人肥大细胞(MC)在IgE致敏过程中、通过IgE激活过程中的miRNA谱,并将其与前列腺素D2合成和组胺释放相关联。
我们研究了从过敏性哮喘患者和非特应性对照中分离的CD133 +干细胞培养的MC在IgE介导的致敏和激活过程中762种miRNA的表达模式。
IgE介导的致敏使miRNA-210的表达增加了8倍。在IgE介导的MC激活过程中,这种增加持续存在。此外,我们证实了MC激活后miRNA-132/212簇的增加。miRNA-210/132/212的预测靶基因在已知参与MC激活的几种途径中富集。与对照组相比,过敏性患者的MC中组胺释放明显更高,并且在MC激活过程中有多种miRNA与组胺释放和前列腺素D2合成相关。
本文介绍的miRNA及其分析有助于阐明miRNA在MC激活过程中介质释放中的作用。我们推测miRNA-210在导致过敏症状的MC致敏中可能很重要。