sphingosine-kinase and Periodontitis

Sphingosine-1-phosphate (S1P) is a pleiotropic sphingophospholipid generated from the phosphorylation of sphingosine by sphingosine kinases (SPHKs). S1P has been experimentally demonstrated to modulate an array of cellular processes such as cell proliferation, cell survival, cell invasion, vascular maturation, and angiogenesis by binding with any of the five known G-protein-coupled sphingosine 1 phosphate receptors (S1P1-5) on the cell surface in an autocrine as well as a paracrine manner. Recent studies have shown that the S1P receptors (S1PRs) and SPHKs are the key targets for modulating the pathophysiological consequences of various debilitating diseases, such as cancer, sepsis, rheumatoid arthritis, ulcerative colitis, and other related illnesses. In this article, we recapitulate these novel discoveries relative to the S1P/S1PR axis, necessary for the proper maintenance of health, as well as the induction of tumorigenic, angiogenic, and inflammatory stimuli that are vital for the development of various diseases, and the novel therapeutic tools to modulate these responses in oral biology and medicine.

Topics: Animals; Atherosclerosis; Autoimmune Diseases; Cell Proliferation; Gene Expression Regulation, Enzymologic; GTP-Binding Protein alpha Subunits; GTP-Binding Protein Regulators; Humans; Lymphatic Metastasis; Lysophospholipids; Mandibular Condyle; Neovascularization, Pathologic; Neurogenic Inflammation; Periodontitis; Phosphotransferases (Alcohol Group Acceptor); Receptors, Lysosphingolipid; Signal Transduction; Sphingosine

This study evaluated changes in the levels of Sphingosine-1-Phosphate (S1P) and Sphingosine Kinase (SPHK) activity in response to non-surgical periodontal treatment in humans.. Diseased (n = 65) and healthy sites (n = 72) were screened in 18 patients with localized periodontitis stage II or III. Periodontal clinical parameters were recorded, and the gingival crevicular fluid (GCF) collected at baseline, 30 and 90 days of non-surgical treatment. Internal control sites without attachment loss/bleeding were sampled at baseline and after 90 days of treatment. SPHK activity and S1P levels and SPHK 1/2 isoforms were determined in the GCF at different time points using ELISA.. Non-surgical treatment caused significant improvement in all periodontal clinical parameters (p < 0.01). Activity of SPHK and S1P levels was decreased (p < 0.05) 30 days after treatment and continued up to 90 days (p < 0.01); control sites remained unchanged throughout the study and resembled treated sites at 3 months (p > 0.05). SPHK1 levels presented decrease after periodontal treatment (p < 0.001). SPHK2 levels were lower than SPHK1 (p < 0.001) and remained unchanged.. S1P levels and SPHK activity decreased within 3 months of non-surgical periodontal treatment, which were correlated with improvements in periodontal parameters. Only SPHK1 levels varied significantly in the states of health and disease.

Topics: Humans; Lysophospholipids; Periodontitis; Periodontium; Phosphotransferases (Alcohol Group Acceptor)