Identification of Differentially Expressed Long Non-coding RNAs in Polarized Macrophages

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-gamma + LPS) or M(IL-4) phenotypes. Compared with primary MDMs, 9343 lncRNAs and 5903 mRNAs were deregulated in M(IFN-gamma + 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-gamma + LPS) macrophages than in M(IL-4) macrophages. TCONS_ 00019715 expression was decreased when M(IFN-gamma + LPS) converted to M(IL-4) whereas increased when M(IL-4) converted to M(IFN-gamma + LPS). Knockdown of TCONS_ 00019715 following the activation of THP-1 cellls using IFN-gamma and LPS diminished the expression of M(IFN-gamma + 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.