Anti‐inflammatory roles of microRNA 21 in lipopolysaccharide‐stimulated human dental pulp cells. Issue 11 (1st May 2019)

• Record Type: Journal Article
• Authors: Nara, Keisuke; Kawashima, Nobuyuki; Noda, Sonoko; Fujii, Mayuko; Hashimoto, Kentaro; Tazawa, Kento; Okiji, Takashi
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 11(2019:Nov.)
• Page Start: 21331
• Page End: 21341
• Publication Date: 2019-05-01
• Subjects: anti‐inflammation -- dental pulp cell -- microRNA 21 -- NF‐κB signaling pathway -- proinflammatory cytokine; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28737
• Languages: English
• ISSNs: 0021-9541

Abstract

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 anti‐inflammatory 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 receptor‐associated 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 inhibitor‐transfected 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. Abstract : Lipopolysaccharide (LPS) stimulation induced both miR‐21‐5p and proinflammatory cytokine expression in human dental pulp cells (hDPCs). miR‐21‐5p negatively regulated the expression of proinflammatory cytokines and the expression of TNF receptor‐associated factor 6 (TRAF6) and programmed cell death 4 (PDCD4), positive regulators of NF‐κB signaling. These findings suggest that miR‐21‐5p may modulate inflammation via inhibition of NF‐κB signaling in LPS‐stimulated human dental pulp cells.