Anti‐inflammatory roles of microRNA 21 in lipopolysaccharide‐stimulated human dental pulp cells

Abstract

microRNAs are small noncoding RNA molecules that regulate RNA silencing and posttranscriptional gene expression, and many microRNAs are involved in inflammatory processes. In particular, microRNA 21 (miR-21) is upregulated in inflammatory environment and reported to induce anti-inflammatory responses. However, the involvement of miR-21 in pulpal inflammation and the precise mechanisms of antiinflammatory reactions induced by miR-21 remain unclear. We hypothesized that miR-21-5p expression is induced in lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs) and that miR-21-5p downregulates the proinflammatory cytokine expression in LPS-stimulated hDPCs. We found that miR-21-5p was upregulated in LPS-stimulated hDPCs concomitant with elevated proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) phosphorylation. miR-21-5p and cytokine expression were downregulated by BAY11-7085 and caffeic acid phenylethyl ester (CAPE), specific and potent NF-κB inhibitors. Enforced expression of miR-21-5p downregulated the Toll-like receptor (TLR)/NF-κB signaling via reducing the expression of TNF receptor-associated factor 6 (TRAF6) and programmed cell death 4 (PDCD4), which further induced the decrease of proinflammatory cytokine expression. hDPCs forcibly overexpressing miR-21-5p downregulated the LPS-induced expression of TNF receptorassociated factor 6 (TRAF6; a component of the Toll-like receptor [TLR]/NF-κB signaling pathway), programmed cell death 4 (PDCD4, a positive regulator of the TLR/NF-κB signaling pathway), and proinflammatory cytokines. In contrast, miR-21-5p inhibitortransfected hDPCs upregulated the expression of TRAF6, PDCD4, and inflammatory cytokines following LPS stimulation. These findings suggest that miR-21-5p expression was induced by the NF-κB signaling pathway, which was in turn negatively regulated by miR-21-5p via downregulation of TRAF6 and PDCD4 expression in LPS-stimulated hDPCs.

Bone marrow mesenchymal stem cells and their derived exosomes resolve doxorubicin-induced chemobrain: critical role of their miRNA cargo

“…Beneficially, BMSCs and BMSCs-Exo successfully revoked this activated immune-inflammatory state with its deleterious sequels in DOX-induced chemobrain via decreasing hippocampal IL-6 and TNF-α levels. This effect is suggested to be through the increased abundance of miR-21-5p in the exosomal BMSCs as discovered by our IPA analysis, which is known for its anti-inflammatory role as agreed by previous studies [ 81 , 82 ]. This anti-inflammatory state leads to a significant decrease in the activated microglia in the brain and the activated astrocytes evidenced by a significant decrease in the IBA-1 and GFAP expression.…”

Age-dependent impairment of adipose-derived stem cells isolated from horses

“…Moreover, miR-146a reduces the production of IL-1β and IL-6 in B cells by targeting IL-1 receptor-associated kinase 1 (IRAK1) but not TNF receptor-associated factor 6 (TRAF6) [71]. Otherwise, miR-21 reduces the activity of the Toll-like receptor (TLR)/NF-κB signaling pathway via the downregulation of TRAF6 [72]. On the contrary, miR-24 inhibits NF-κB nuclear translocation and biosynthesis of TNF-α and IL-6 [73].…”

Target Dependent Coordinated Biogenesis Ensures Cascaded Expression of miRNAs in Activated Murine Macrophage

“…Confirming the loss of miR-142-3pactivity in absence of active miR-146-5p to repress the IRAK1 (Figure 1L). miR-21 is another critical modulator of LPS-responsive pathways (Sheedy et al, 2010).TARGETSCAN and previous reports also reveal 3' UTR of both the TRAF6 and IRAK1 mouse mRNA contains single miR-21-5p binding sites along with miR-146a-5p (Figure S1C-D) (Agarwal et al, 2015;Nara et al, 2019).…”