Mechanism of miRNA-based Aconitum leucostomum Worosch. Monomer inhibition of bone marrow-derived dendritic cell maturation

Delvestidine (DLTD) is a monomeric compound isolated from Aconitum leucostomum Worosch, a widely used medicine for local treatment of rheumatoid arthritis (RA). Studies have shown that Aconitum leucostomum Worosch. can inhibit maturation of bone marrow-derived dendritic cells (BMDCs). Further, microRNAs (miRNAs) have regulatory effects on DC maturity and function. However, the mechanism underlying DLTD effects on DC maturity and RA remains to be elucidated. This study investigated whether DLTD-mediated inhibition of DC maturation is regulated by miRNAs. LPS-induced mature BMDCs were treated with DLTD for 48 h. CD80 and CD86 expression on BMDCs was detected by flow cytometry, and levels of inflammatory factors IL-6, IL-23, IL-1β, and TNF-α were detected by ELISA and PCR. Further, gene expression and miRNA expression profiles were investigated by bioinformatics analysis and verified by PCR. DLTD was found to inhibit CD80 and CD86 expression on the surface of BMDCs and secretion of inflammatory factors IL-6, IL-23, IL-1β, and TNF-α. In total, 54 differentially expressed miRNAs were detected, including 29 up-regulated and 25 down-regulated miRNAs after DLTD treatment. Analysis of biological information revealed that the differentially expressed target genes mainly regulated biological processes, including cell differentiation, cell cycle, and protein kinase complexes. Additionally, miR-511-3p downstream targets Calcr, Fzd10, and Eps8, were closely related to BMDCs maturation. DLTD may induce BMDCs maturity through regulation of miRNAs that affect Calcr, Fzd10, and Eps8 gene signals.

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