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

Abstract

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.

Microarray profiling identifies extracellular circulating miRNAs dysregulated in cystic fibrosis

“…Let-7b is one of the most studied of the let-7 miRNA family and its functional role has been characterized in some cell types. For example, let-7b was demonstrated to regulate immunity-related genes such as IL6 and TNF in monocytes and SERPINE1 in lipopolysaccharide-induced macrophages 31 , implying that let-7b dysregulation in cells may impair immune responses to pathogenic agents. Let-7b was also demonstrated to be involved in regulating the activation of hepatic stellate cells by interacting with lin28 in human alcoholic liver disease 32 .…”

Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder

“…MiR-155 plays an important role in inflammatory response. This miRNA modulates differentiation and activation of cells playing a crucial role in innate and adaptive immune systems [42]. However, contrasting findings have been reported as regard to the role of miR-155, with some studies suggesting it to be part of a negative feedback loop which downregulates synthesis of inflammatory cytokines [43] and other reports suggesting a putative pro-inflammatory role [42].…”

Effects of Omega-3 Fatty Acids on Immune Cells

“…It has been shown that DHA and other ALA derivatives decrease ROS and NO production [33,47] in LPS-stimulated macrophages, which could be associated with decreased transcription factor activation. Also, DHA and EPA have been found to regulate miRNA expression in Raw and THP-1-derived macrophages that could add an additional regulatory level of the inflammatory transcription factors [25,48].…”