Emerging role of microRNAs in regulating macrophage activation and polarization in immune response and inflammation

Abstract

SummaryDiversity and plasticity are hallmarks of macrophages. Classically activated macrophages are considered to promote T helper type 1 responses and have strong microbicidal, pro-inflammatory activity, whereas alternatively activated macrophages are supposed to be associated with promotion of tissue remodelling and responses to anti-inflammatory reactions. Transformation of different macrophage phenotypes is reflected in their different, sometimes even opposite, roles in various diseases or inflammatory conditions. MicroRNAs (miRNAs) have emerged as critical regulators of macrophage polarization (MP). Several miRNAs are induced by Toll-like receptors signalling in macrophages and target the 3 0 -untranslated regions of mRNAs encoding key molecules involved in MP. Therefore, identification of miRNAs related to the dynamic changes of MP and understanding their functions in regulating this process are important for discussing the molecular basis of disease progression and developing novel miRNA-targeted therapeutic strategies. Here, we review the current knowledge of the role of miRNAs in MP with relevance to immune response and inflammation.

Monocyte-Macrophages and T Cells in Atherosclerosis

“…Macrophage functions can vary widely depending on a number of interacting variables and factors, including local environment (“tissue niche”) (Gosselin et al, 2014; Lavin et al, 2014); intracellular energy metabolism (Van den Bossche et al, 2017); gut microbiota metabolites (Wang et al, 2011); and genetic and epigenetic factors, including non-coding RNAs (Erbilgin et al, 2013; Chen et al, 2015; Wu et al, 2016; Amit et al, 2016; Phan et al, 2017; Aryal et al, 2014). These factors program macrophages for functions on a spectrum from inflammatory and host defense to resolution and repair.…”

Macrophages and the Recovery from Acute and Chronic Inflammation

“…The miRNA-146 family of miRNAs, consisting of miRNA-146a and miRNA-146b, consists of negative feedback regulators of TLR signaling. miRNA-146a targets IRAK1, TRAF6, IRAK2, and IRF5, and miRNA-146b targets TLR4, MyD88, IRAK1, and TRAF6 (47). miRNA-146b is an IL-10-dependent miRNA that regulates the LPS-mediated proinflammatory cytokine secretion of TNF-α, IL-6, and IL-8 and chemokines CCL2, CCL3, and IP-10 (48).…”

MicroRNA-155 is upregulated in ascites in patients with spontaneous bacterial peritonitis

“…They were described as small, non-coding RNA’s of about 21–25 nucleotides7. They regulate gene expression by binding to messenger RNA (mRNA)8 and are thereby implicated in essential biological processes, among them liver disease8 and inflammation910. In addition, due to their size and ability to circulate they are regarded as potential biomarkers for a variety of diseases including liver disease11121314.…”

“…MiR-125b and miR-155 are both involved in macrophage activation1015, which are next to lymphocytes the predominant cell population in ascites16. In murine peritoneal macrophages, miR-125b was upregulated after induction of peritonitis and re-stimulation with lipopolysaccharide (LPS); it was identified as a potential mediator of tolerance to LPS17.…”