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Localization of the Platelet‐Activating Factor Receptor on the Intact Human Periodontal Ligament
Author(s) -
Cerutis D. Roselyn,
Nichols Michael G.,
Khan Shakeel A.,
Miyamoto Takanari
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb24
Subject(s) - lysophosphatidic acid , periodontal fiber , receptor , chemistry , g protein coupled receptor , microbiology and biotechnology , confocal microscopy , mediator , signal transduction , biochemistry , medicine , biology , dentistry
Our laboratory has reported the presence of the lysophosphatidic acid receptor subtypes (LPARs) LPA1 and LPA3 on the intact human periodontal ligament (huPDL) using an in situ technique we developed (Cerutis et al. 2016). PAF (platelet‐activating factor) is another lipid mediator that also plays key homeostatic and inflammatory roles. Like LPA, it acts at nM concentrations and is found in significantly higher concentrations in saliva and gingival crevicular fluid from patients with chronic periodontal disease (PD), as we have reported for LPA (Bathena et al. 2011). It is now established that members of the LPA, PAF and prostaglandin (EP) GPCRs can localize to the nucleus in mammals (Gobeil et al., 2003).The LPAR and PAFR GPCRs are expressed in nuclear membranes in other systems, where they share signal transduction pathways to activate inflammatory gene transcription like COX‐2 and inducible nitric oxide synthase. Therefore, we hypothesized that the PAFR would also be expressed throughout healthy and PD PDL, where they would likely interact with LPARs to regulate the inflammatory response to periodontal pathogens. Methods Polyclonal antibodies (Abs) against LPA3 and PAFR were covalently tagged with R‐Phycoerythrin and used to label both receptors on PDL from healthy and PD patients (IRB‐approved, consented donors), using our in situ technique. Results Confocal microscopy confirmed nuclear LPA3, and nuclear labeling was detected with PAFR Abs; similar but different patterns of distribution were seen for each GPCR. In conclusion, to the best of our knowledge, this is the first report of the presence of the PAFR on intact huPDL. In inflamed periodontal tissue, PAF may play a significant role, as it induces vasodilation and platelet aggregation; LPA is produced by activated platelets, so they are likely to interact at the molecular level. We reported that LPA regulates the expression of >60 PD‐associated inflammatory transcripts in human oral fibroblasts (Cerutis et al. 2015), supporting LPARs as having a regulatory role in chronic PD. This confirmed presence of PAFRs on the huPDL suggests that further investigation of the interplay of these two receptor families is needed to determine their role in both PDL homeostasis and in chronic PD.