MiR-885-3p is down-regulated in peripheral blood mononuclear cells from T1D patients and regulates the inflammatory response via targeting TLR4/NF-κB signaling.

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive destruction of insulin-production pancreatic β cells. Recently, microRNAs (miRNAs) have emerged as important regulators in T1D. The present study aimed to determine miR-885-3p expression in T1D patients and to examine the effects of miR-885-3p on the inflammatory response in human monocytes. Relevant gene expression levels were determined by a quantitative polymerase chain reaction; western blotting and enzyme-linked immunosorbent assays determined the respective protein levels; and the interaction between miRNA and the downstream targets was evaluated using a luciferase reporter assay. MiR-885-3p is down-regulated and the levels of pro-inflammatory cytokines are increased in peripheral blood mononuclear cells (PBMCs) from T1D patients compared to healthy controls. MiR-885-3p overexpression suppressed mRNA expression and secreted protein levels of pro-inflammatory cytokines in THP-1. A luciferase reporter assay showed that miR-885-3p directly targeted the 3'-untranslated region of Toll-like receptor 4 (TLR4) and miR-885-3p overexpression down-regulated TLR4 expression in THP-1 cells. The TLR4 mRNA expression level was increased in PBMCs isolated from T1D patients compared to heathy controls. TLR4 overexpression increased the secretion of pro-inflammatory cytokines and enhanced the activity of NF-κB signaling, and also attenuated the inhibitory effects of miR-885-3p overexpression on pro-inflammatory cytokine secretion and the activity of NF-κB signaling in THP-1 cells. The present study identified the down-regulation of miR-885-3p and up-regulation of TLR4 in PBMCs isolated from T1D patients. Further mechanistic data demonstrated that miR-885-3p overexpression represses the production of pro-inflammatory cytokines via targeting TLR4/NF-κB signaling in THP-1 cells.