MicroRNA-155 and macrophages: a fatty liaison

This editorial refers to ‘Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis’ by F.-J. Tian et al. , pp. 100–110, this issue. The inflammatory activation of lipid-loaded macrophages in the arterial intima plays a major role in the pathogenesis of atherosclerosis.1 The unrestricted uptake of oxidatively modified low-density lipoprotein (oxLDL) via scavenger receptors results in the storage of cholesterol esters in lipid droplets in macrophages due to the limited efflux of free cholesterol.1 However, free cholesterol can accumulate in the membrane of the endoplasmic reticulum (ER), which triggers ER stress and inflammatory activation. Moreover, cholesterol crystals may form and induce the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and IL-1β production.2 Nevertheless, it is still incompletely understood how cholesterol accumulation triggers inflammation in macrophages. A distinct subset of small non-coding RNAs (miRNAs), including miR-155 and miR-146, regulates the inflammatory signalling pathways in macrophages by translational repression or degradation of their target mRNAs.3 Activation of various Toll-like receptors (TLR) induces miR-155 expression via myeloid differentiation primary response gene (MyD88)- or toll-interleukin-1 receptor (TIR) domain-containing adapter-inducing IFN-β-dependent signalling, probably through NF-κB activation.4 Moreover, mildly oxidized LDL, which can bind to TLR4, in combination with IFN-γ induces the expression of miR-155 …