Lenart Marzena, Rutkowska-Zapała Magdalena, Szatanek Rafał, Węglarczyk Kazimierz, Stec Małgorzata, Bukowska-Strakova Karolina, Gruca Anna, Czyż Jarosław, Siedlar Maciej
Department of Clinical Immunology, Institute of Paediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Immunobiology. 2017 Mar;222(3):494-498. doi: 10.1016/j.imbio.2016.10.016. Epub 2016 Oct 18.
Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16 monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14CD16), intermediate (CD14CD16) and non-classical (CD14CD16) monocytes, as well as during in vitro differentiation of the isolated monocytes towards dendritic cells or macrophages. Our results revealed that the level of TRIM21 mRNA expression was significantly lower in CD16- monocytes, when compared to CD16 cells and the whole monocyte population, yet no significant differences were observed when CD16 population was divided into intermediate and non-classical subsets. More pronounced differences were observed in the case of monocyte-derived macrophages (MDM) and dendritic cells (DCs). TRIM21-mRNA expression level was app. 6-fold higher in DCs, and app. 16-fold higher in MDM (p<0,01), when compared to freshly isolated monocytes. Our results may suggest the new mechanism of increased proinflammatory cytokine production by CD16 (intermediate and non-classical) monocytes and macrophages, at least in patients with acute or chronic infections, caused by enveloped viruses. We suggest that TRIM21 may be one of the factors associated with the "switching on" the proinflammatory programme in CD16 monocytes or monocyte-derived macrophages.
含三联基序蛋白21(TRIM21)在细胞胞质中发挥双重作用,它促进一些抗体包被的病毒和一些细菌的破坏,并启动促炎细胞因子的合成。巨噬细胞和CD16单核细胞亚群尤其可参与由病毒感染引起的促炎反应,然而,这些过程背后的分子机制尚未完全明确。本研究的目的是确定TRIM21 - mRNA在单核细胞亚群(包括经典型(CD14⁺CD16⁻)、中间型(CD14⁺CD16⁺)和非经典型(CD14⁻CD16⁺)单核细胞)中的表达水平,以及在体外分离的单核细胞向树突状细胞或巨噬细胞分化过程中的表达水平。我们的结果显示,与CD16⁺细胞和整个单核细胞群体相比,CD16⁻单核细胞中TRIM21 mRNA的表达水平显著降低,然而,当将CD16⁺群体分为中间型和非经典型亚群时,未观察到显著差异。在单核细胞衍生的巨噬细胞(MDM)和树突状细胞(DC)中观察到更明显的差异。与新鲜分离的单核细胞相比,DC中TRIM21 - mRNA的表达水平约高6倍,MDM中约高16倍(p<0.01)。我们的结果可能提示了CD16⁺(中间型和非经典型)单核细胞和巨噬细胞促炎细胞因子产生增加的新机制,至少在由包膜病毒引起的急性或慢性感染患者中如此。我们认为TRIM21可能是与CD16单核细胞或单核细胞衍生的巨噬细胞中促炎程序“开启”相关的因素之一。