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Published on: October 27, 2023
MicroRNA-27a-5p Downregulates Expression of Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Human Dental
Shihan Wang1, Nobuyuki Kawashima1, Peifeng Han1
1Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan.
Abstract:
MicroRNA-27a-5p (miR-27a-5p) was significantly upregulated in dental pulp inflammation, yet its underlying mechanisms remain unclear. This study investigated the effect of miR-27a-5p on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS). LPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-κB inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated the expression of proinflammatory cytokines, NF-κB activity, and the expression of NF-κB signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3'-UTR of TAB1. siTAB1 downregulated NF-κB activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-κB activity, and NF-κB signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimic ex vivo. MiR-27a-5p, whose expression was induced by NF-κB signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-κB signaling. In particular, TAB1, a potent NF-κB activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-κB signaling pathway, on pulp inflammation.
Insights
MicroRNA-27a-5p (miR-27a-5p) reduces dental pulp inflammation by targeting the TAB1-NF-κB pathway. This microRNA downregulates key inflammatory cytokines, offering potential therapeutic insights.
Area of Science:
- Biomedical Science
- Molecular Biology
- Immunology
Background:
- Dental pulp inflammation involves increased microRNA-27a-5p (miR-27a-5p) expression.
- The precise mechanisms by which miR-27a-5p influences pulp inflammation are not fully understood.
Purpose of the Study:
- To investigate the role of miR-27a-5p in regulating proinflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs).
- To elucidate the molecular mechanisms underlying miR-27a-5p's effect on the NF-κB signaling pathway in dental pulp inflammation.
Main Methods:
- LPS stimulation of hDPCs and rat incisor pulp tissue explants.
- Transfection with miR-27a-5p mimic and small interfering RNA (siTAB1).
- Measurement of cytokine levels (IL-6, IL-8, MCP1), NF-κB activity, and expression of signaling molecules (TAB1, IRAK4, RELA, FSTL1).
- Luciferase reporter assays to confirm direct targeting of TAB1 by miR-27a-5p.
Main Results:
- LPS upregulated miR-27a-5p, proinflammatory cytokines, and NF-κB activity in hDPCs.
- miR-27a-5p mimic transfection downregulated cytokine expression, NF-κB activity, and key NF-κB signaling activators.
- miR-27a-5p directly targets the 3'-UTR of TAB1, a crucial NF-κB activator.
- Similar suppressive effects were observed in ex vivo LPS-stimulated rat pulp tissue.
Conclusions:
- MiR-27a-5p negatively regulates proinflammatory cytokine synthesis in dental pulp cells by targeting the TAB1-NF-κB signaling pathway.
- NF-κB signaling induces miR-27a-5p expression, which in turn dampens the inflammatory response.
- Targeting the miR-27a-5p/TAB1/NF-κB axis presents a potential therapeutic strategy for dental pulp inflammation.
