Huang Zikun, Luo Qing, Yao Fangyi, Qing Cheng, Ye Jianqing, Deng Yating, Li Junming
Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
Department of Clinical Laboratory, Jiangxi Province Blood Center, Nanchang 330006, Jiangxi, China.
Sci Rep. 2016 Jan 22;6:19705. doi: 10.1038/srep19705.
Macrophages display remarkable plasticity, with the ability to undergo dynamic transition between classically and alternatively activated phenotypes. Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and play roles in various biological pathways. However, the role of lncRNAs in regulating macrophage polarization has yet to be explored. In this study, lncRNAs expression profiles were determined in human monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M(IFN-γ + LPS) or M(IL-4) phenotypes. Compared with primary MDMs, 9343 lncRNAs and 5903 mRNAs were deregulated in M(IFN-γ + LPS) group (fold change ≥ 2.0, P < 0.05), 4592 lncRNAs and 3122 mRNAs were deregulated in M(IL-4) group. RT-qPCR results were generally consistent with the microarray data. Furthermore, we found that TCONS_00019715 is expressed at a higher level in M(IFN-γ + LPS) macrophages than in M(IL-4) macrophages. TCONS_00019715 expression was decreased when M(IFN-γ + LPS) converted to M(IL-4) whereas increased when M(IL-4) converted to M(IFN-γ + LPS). Knockdown of TCONS_00019715 following the activation of THP-1 cellls using IFN-γ and LPS diminished the expression of M(IFN-γ + LPS) markers, and elevated the expression of M(IL-4) markers. These data show a significantly altered lncRNA and mRNA expression profile in macrophages exposure to different activating conditions. Dysregulation of some of these lncRNAs may play important roles in regulating macrophage polarization.
巨噬细胞表现出显著的可塑性,能够在经典激活型和交替激活型表型之间进行动态转变。长链非编码RNA(lncRNA)长度超过200个核苷酸,并在各种生物学途径中发挥作用。然而,lncRNA在调节巨噬细胞极化中的作用尚未得到探索。在本研究中,我们测定了在诱导向M(IFN-γ + LPS)或M(IL-4)表型激活的条件下培养的人单核细胞衍生巨噬细胞(MDM)中的lncRNA表达谱。与原代MDM相比,M(IFN-γ + LPS)组中有9343个lncRNA和5903个mRNA表达失调(倍数变化≥2.0,P < 0.05),M(IL-4)组中有4592个lncRNA和3122个mRNA表达失调。RT-qPCR结果与微阵列数据总体一致。此外,我们发现TCONS_00019715在M(IFN-γ + LPS)巨噬细胞中的表达水平高于M(IL-4)巨噬细胞。当M(IFN-γ + LPS)转变为M(IL-4)时,TCONS_00019715的表达降低,而当M(IL-4)转变为M(IFN-γ + LPS)时,其表达增加。使用IFN-γ和LPS激活THP-1细胞后敲低TCONS_00019715可降低M(IFN-γ + LPS)标志物的表达,并提高M(IL-4)标志物的表达。这些数据表明,巨噬细胞在暴露于不同激活条件下时,lncRNA和mRNA表达谱发生了显著改变。其中一些lncRNA的失调可能在调节巨噬细胞极化中发挥重要作用。