Regulatory roles of miR-155 and let-7b on the expression of inflammation-related genes in THP-1 cells: effects of fatty acids

• Published in: Journal of physiology and biochemistry Vol. 74; no. 4; pp. 579 - 589
• Main Authors: Marques-Rocha, J.L., Garcia-Lacarte, M., Samblas, M., Bressan, J., Martínez, J.A., Milagro, F.I.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2018; Springer Nature B.V
• Subjects: Acetic acid; Acute monocytic leukemia; Animal Physiology; Biomedical and Life Sciences; Biomedicine; Cell Differentiation - drug effects; Docosahexaenoic Acids - metabolism; Down-Regulation; Fatty acids; Fatty Acids, Nonesterified - metabolism; Gene expression; Gene Expression Regulation - drug effects; Genes; Human Physiology; Humans; Immune system; Inflammation; Interleukin 6; Interleukin-6 - agonists; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipopolysaccharides; Lipopolysaccharides - toxicity; Macrophage Activation - drug effects; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; MicroRNAs - chemistry; MicroRNAs - metabolism; miRNA; Monocytes; Monocytes - immunology; Monocytes - metabolism; Monocytic leukemia; Oleic acid; Oleic Acid - metabolism; Original Article; Plasminogen Activator Inhibitor 1 - agonists; Plasminogen Activator Inhibitor 1 - chemistry; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; RNA - metabolism; Tetradecanoylphorbol Acetate - pharmacology; THP-1 Cells; TLR4 protein; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - agonists; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Monocytes; Macrophages; DHA; Oleic acid; SERPINE1; EPA
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-018-0629-x

The main aim of this investigation was to study the regulatory roles of let-7b and miR-155-3p on the expression of inflammation-associated genes in monocytes, macrophages, and lipopolysaccharide (LPS)-activated macrophages (AcM). A second goal was to analyze the potential modulatory roles of different fatty acids, including oleic, palmitic, eicosapentaenoic (EPA), and docosahexaenoic (DHA), on the expression of these miRNAs in the three cell types. This hypothesis was tested in human acute monocytic leukemia cells (THP-1), which were differentiated into macrophages with 2-O-tetradecanoylphorbol-13-acetate (TPA) and further activated with LPS for 24 h. Monocytes, macrophages, and AcM were transfected with a negative control, or mimics for miR-155-3p and miR-let-7b-5p. The expression of both miRNAs and some proinflammatory genes was analyzed by qRT-PCR. Interestingly, let-7b mimic reduced the expression of IL6 and TNF in monocytes, and SERPINE1 expression in LPS-activated macrophages. However, IL6 , TNF , and SERPINE1 were upregulated in macrophages by let-7b mimic. IL6 expression was higher in the three types of cells after transfecting with miR-155-3p mimic. Similarly, expression of SERPINE1 was increased by miR-155-3p mimic in monocytes and macrophages. However, TLR4 was downregulated by miR-155-3p in monocytes and macrophages. Regarding the effects of the different fatty acids, oleic acid increased the expression of let-7b in macrophages and AcM and also increased the expression of miR-155 in monocytes when compared with DHA but not when compared with non-treated cells. Overall, these results suggest anti- and proinflammatory roles of let-7b and miR-155-3p in THP-1 cells, respectively, although these outcomes are strongly dependent on the cell type. Noteworthy, oleic acid might exert beneficial anti-inflammatory effects in immune cells (i.e., non-activated and LPS-activated macrophages) by upregulating the expression of let-7b.