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RvD1n-3 DPA downregulates transcription of pro-inflammatory genes in oral epithelial cells and reverses nuclear translocation of transcription factor p65 after TNF-α stimulation

ABSTRACT: Specialized pro-resolving mediators (SPMs) are multifunctional lipid mediators that participate in the resolution of inflammation. We have recently described that oral epithelial cells (OECs) express receptors of the SPM resolvin RvD1n-3 DPA and that cultured OECs respond to the RvD1n-3 DPA addition by intracellular calcium release, nuclear receptor translocation and transcription of genes coding for antimicrobial peptides. The aim of the present study was to assess the functional outcome of RvD1n-3 DPA–signaling in OECs. under inflammatory conditions. To this end, we performed transcriptomic analyses of TNF-α-stimulated cells that were subsequently treated with RvD1n-3 DPA and found significant downregulation of pro-inflammatory nuclear factor kappa B (NF-κB) target genes. Further bioinformatics analyses also showed that RvD1n-3 DPA inhibited expression of several genes involved in the NF-κB activation pathway. Immunofluorescence examination revealed that addition of RvD1n-3 DPA to OECs reversed TNF-α-induced nuclear translocation of NF-κB p65. Co-treatment of the cells with the exportin 1 inhibitor leptomycin B indicated that RvD1n-3 DPA increases nuclear export of p65. Unlike earlier cell cultural studies where SPMs are added before or together with the inflammatory stimulus, the present observations suggest that SPMs also have the potential to be used as a therapeutic aid when inflammation is established.

ORGANISM(S): Homo sapiens

PROVIDER: GSE215275 | GEO | 2022/10/14

REPOSITORIES: GEO

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