Abstract
The primary function of toll-like receptor 8 (TLR-8) is the detection of viruses and other microbial pathogens. Recent evidence suggests that TLR-8 also senses host microRNAs (miRNAs) and implicate TLR-8 in autoimmune disorders. This study examined the interaction between miR-1294 and TLR-8. We first performed a BLAST search to identify miRNAs with the same sequences as two core motifs of miR-1294. Next, we examined NFḱB activation induced by the binding of miR-1294 mimic to endosomal TLR-8. HEK-Blue™ hTLR-8 cells (Invivogen), a HEK293 cell line co-transfected with human TLR-8 gene, were incubated with miR-1294 mimic. A TLR-8 agonist ssRNA40, was used as a positive control. Using the same experimental set up, we also examined the effects of miR-1294 and its two core motifs (Integrated DNA Technologies) on IL-8, IL-1β, and TNFα. Data were analyzed using t-test or one-way ANOVA and Dunnets post-hoc test. Using miRCarta we identified 29 other mature human miRNAs or their precursors which contain the same core motifs as miR-1294. Our data show that miR-1294 activates NFḱB in cells expressing TLR-8 (p < 0.05). miR-1294, and its core motifs induce expression of IL-8, IL-1β, and TNFα via TLR8 activation (p < 0.05). This constitutes a novel mechanism by which endosomal TLR-8 senses host miRNAs resulting in the release of pro-inflammatory cytokines and thus potentially contributing to autoimmune disorders.
Highlights
Pathogen-associated molecular pattern receptors, including toll-like receptors (TLRs), are key molecules in the response to pathological stimuli such as bacterial endotoxins
toll-like receptor 8 (TLR-8) is primarily miRNA1294 Activates TLR-8 expressed in monocytes, myeloid dendritic cells, and neutrophils while TLR-7 is expressed in B cells and plasmacytoid dendritic cells [10,11,12]
The current study examined whether TLR-8 is activated by miR1294 and its core motifs resulting in the production of proinflammatory cytokines
Summary
Pathogen-associated molecular pattern receptors, including toll-like receptors (TLRs), are key molecules in the response to pathological stimuli such as bacterial endotoxins. TLRs are ubiquitously expressed by immune and non-immune cells including neurons, fibroblasts, endothelial cells, epithelial cells, and adipocytes. They recognize viral and microbial structures, and some endogenous molecules such as single stranded RNAs [1,2,3]. Classic activation of TLRs depends upon the pathogen and the TLR expressing cell subtype [4]. Some TLRs, TLRs 7, 8, and 9, recognize self molecules such as single stranded RNAs and play a role in autoimmunity. TLR-8 is primarily miRNA1294 Activates TLR-8 expressed in monocytes, myeloid dendritic cells, and neutrophils while TLR-7 is expressed in B cells and plasmacytoid dendritic cells [10,11,12]. Unlike TLR-7, TLR-8 senses ssRNA through its ability to form secondary structures [13]
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