MiR-216a-5p-containing exosomes suppress rTp17-induced inflammatory response by targeting TLR4

Area of Science:

• Infectious Diseases
• Molecular Biology
• Immunology

Background:

• Syphilis, caused by *Treponema pallidum*, is a global health concern with rising incidence and associated tissue inflammation.
• MicroRNA (miRNA)-containing exosomes are emerging as therapeutic targets for various diseases.
• The role of miR-216a-5p in syphilis pathogenesis was previously unknown.

Purpose of the Study:

• To investigate the role and mechanism of miR-216a-5p in syphilis pathogenesis.
• To explore the potential of miR-216a-5p-containing exosomes as a therapeutic strategy for syphilis-induced inflammation.

Main Methods:

• Quantified miR-216a-5p levels in plasma from syphilis patients and healthy controls.
• Treated endothelial cells with recombinant Tp17 (rTp17) and miR-216a-5p-containing exosomes.
• Assessed inflammatory cytokine expression (IL-1β, IL-6, TNF-α).
• Identified miR-216a-5p binding targets using 3'-untranslated region (UTR) assays and western blotting for the TLR4-MYD88 pathway.

Main Results:

• Syphilis patients exhibited significantly decreased plasma miR-216a-5p levels, negatively correlated with inflammatory cytokines.
• miR-216a-5p-containing exosomes attenuated rTp17-induced inflammatory responses in endothelial cells.
• miR-216a-5p directly targets the 3'-UTR of Toll-like receptor 4 (TLR4).
• Overexpression of TLR4 reversed the suppressive effects of miR-216a-5p on inflammatory cytokine production and the TLR4-MYD88 pathway.

Conclusions:

• This study identifies a novel function of miR-216a-5p in regulating endothelial cell inflammation during syphilis.
• miR-216a-5p acts by targeting TLR4 and inhibiting the TLR4-MYD88 signaling pathway.
• miR-216a-5p-containing exosomes represent a promising therapeutic target for managing inflammation in syphilis.