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

• Published in: The journal of gene medicine 2020-01, Vol.22 (1), p.e3145-n/a
• Main Authors: Zhang, Xiangdong, Gu, Huimin, Wang, Li, Huang, Feng, Cai, Jin
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Beta cells; Cytokines; Diabetes mellitus (insulin dependent); Gene expression; Gene therapy; Inflammation; Insulin; Leukocytes (mononuclear); MicroRNAs; miRNA; miR‐885‐3p; Monocytes; NF‐κB; Pancreas; PBMCs; Peripheral blood mononuclear cells; Polymerase chain reaction; pro‐inflammatory cytokines; TLR4; TLR4 protein; Toll-like receptors; type 1 diabetes; Western blotting
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.3145

Background 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. Methods 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. Results 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. Conclusions 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.