MicroRNA-146b-5p Suppresses Pro-Inflammatory Mediator Synthesis via Targeting TRAF6, IRAK1, and RELA in...

Area of Science:

• Oral Biology
• Immunology
• Molecular Biology

Background:

• MicroRNA-146b-5p (miR-146b-5p) plays a role in inflammation, but its precise mechanisms are not fully understood.
• Dental pulp cells (hDPCs) are crucial in the oral immune response.
• Lipopolysaccharide (LPS) is a potent inducer of inflammation.

Purpose of the Study:

• To investigate the anti-inflammatory effects of miR-146b-5p in LPS-stimulated human dental pulp cells (hDPCs).
• To elucidate the regulatory pathways controlling miR-146b-5p expression and its downstream targets in dental pulp inflammation.

Main Methods:

• LPS stimulation of hDPCs to induce inflammation and measure miR-146b-5p and cytokine expression.
• Use of nuclear factor-kappa B (NF-κB) and Janus kinase (JAK1/2) inhibitors to study signaling pathways.
• Enforced expression of miR-146b-5p to assess its impact on NF-κB signaling components (IRAK1, TRAF6, RELA).
• In vivo studies using a rat model of pulpal inflammation and ex vivo experiments on rat incisor pulp tissues.

Main Results:

• LPS stimulation increased both miR-146b-5p and pro-inflammatory cytokine mRNA expression in hDPCs.
• NF-κB and JAK1/2 inhibitors reduced the expression of miR-146b-5p and pro-inflammatory cytokines.
• Enforced miR-146b-5p expression suppressed NF-κB p65 phosphorylation and down-regulated key NF-κB signaling components (IRAK1, TRAF6, RELA).
• miR-146b-5p expression was upregulated during experimental rat pulpal inflammation, and it inhibited pro-inflammatory mediators in vivo and ex vivo.

Conclusions:

• miR-146b-5p synthesis is regulated by an NF-κB/IL6/STAT3 signaling cascade.
• miR-146b-5p exerts anti-inflammatory effects by targeting TRAF6, IRAK1, and RELA in LPS-stimulated hDPCs.
• These findings highlight miR-146b-5p as a potential therapeutic target for dental pulp inflammation.