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Specialized pro-resolving lipid mediators (SPMs) are known for their anti-inflammatory and pro-resolving actions. The aim of the present study was to find new functions of the SPM resolvin D1 n-3 DPA (RvD1 n-3 DPA ) on oral epithelial cells. As a starting point, we used a dataset obtained by RNA high-throughput sequencing of oral epithelial cells exposed to TNF-α and RvD1 n-3 DPA versus TNF-α alone. GOrilla enrichment analysis showed that the actin cytoskeleton was significantly overrepresented after adjustment for multiple hypothesis testing. As actin, amongst others, is closely related to cell migration, we then explored whether RvD1 n-3 DPA can modulate oral epithelial cell migration. To this end, we used an in vitro cell migration model, including TNF-α treatment, to mimic an inflammatory cell state. The analysis revealed that RvD1 n-3 DPA increased oral epithelial cell migration in the presence but not in the absence of TNF-α. Addition of RvD1 n-3 DPA also induced F actin accumulation around the cell nucleus, indicating that RvD1 n-3 DPA potentially can mediate processes of intracellular transport. This indicates that this lipid mediator may be a promising therapeutic candidate in oral mucosal wound healing., (© 2024 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)

Chronic inflammatory responses can inflict permanent damage to host tissues. Specialized pro-resolving mediators downregulate inflammation but also can have other functions. The aim of this study was to examine whether oral epithelial cells express the receptors FPR2/ALX and DRV1/GPR32, which bind RvD1 n-3 DPA , a recently described pro-resolving mediator derived from omega-3 docosapentaenoic acid (DPA), and whether RvD1 n-3 DPA exposure induced significant responses in these cells. Gingival biopsies were stained using antibodies to FPR2/ALX and DRV1/GPR32. Expression of FPR2/ALX and DRV1/GPR32 was examined in primary oral epithelial cells by qRT-PCR, flow cytometry, and immunofluorescence. The effect of RvD1 n-3 DPA on intracellular calcium mobilization and transcription of beta-defensins 1 and 2, and cathelicidin was evaluated by qRT-PCR. FPR2/ALX and DRV1/GPR32 were expressed by gingival keratinocytes in situ. In cultured oral epithelial cells, FPR2/ALX was detected on the cell surface, whereas FPR2/ALX and DRV1/GPR32 were detected intracellularly. Exposure to RvD1 n-3 DPA induced intracellular calcium mobilization, FPR2/ALX internalization, DRV1/GPR32 translocation to the nucleus, and significantly increased expression of genes coding for beta-defensin 1, beta-defensin 2, and cathelicidin. This shows that the signal constituted by RvD1 n-3 DPA is recognized by oral keratinocytes and that this can strengthen the antimicrobial and regulatory potential of the oral epithelium., (© 2022 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)