Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, Norway.
Eur J Oral Sci. 2022 Aug;130(4):e12883. doi: 10.1111/eos.12883. Epub 2022 Jul 8.
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 , a recently described pro-resolving mediator derived from omega-3 docosapentaenoic acid (DPA), and whether RvD1 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 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 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 is recognized by oral keratinocytes and that this can strengthen the antimicrobial and regulatory potential of the oral epithelium.
慢性炎症反应会对宿主组织造成永久性损伤。专门的促解决介质下调炎症反应,但也可以具有其他功能。本研究旨在检查口腔上皮细胞是否表达受体 FPR2/ALX 和 DRV1/GPR32,这些受体结合 RvD1,一种最近描述的来自 omega-3 二十二碳五烯酸(DPA)的促解决介质,以及 RvD1 暴露是否会引起这些细胞的显著反应。使用针对 FPR2/ALX 和 DRV1/GPR32 的抗体对牙龈活检进行染色。通过 qRT-PCR、流式细胞术和免疫荧光法检查原代口腔上皮细胞中 FPR2/ALX 和 DRV1/GPR32 的表达。通过 qRT-PCR 评估 RvD1 对细胞内钙动员以及β-防御素 1 和 2 和抗菌肽 cathelicidin 的转录的影响。FPR2/ALX 和 DRV1/GPR32 原位表达于牙龈角质形成细胞中。在培养的口腔上皮细胞中,FPR2/ALX 检测到在细胞表面,而 FPR2/ALX 和 DRV1/GPR32 检测到细胞内。RvD1 的暴露诱导细胞内钙动员、FPR2/ALX 内化、DRV1/GPR32 向核移位,并显著增加编码β-防御素 1、β-防御素 2 和抗菌肽 cathelicidin 的基因的表达。这表明 RvD1 构成的信号被口腔角质形成细胞识别,这可以增强口腔上皮的抗菌和调节潜力。