sphingosine-phosphorylcholine and Inflammation

Sjögren syndrome (SS) is an autoimmune disease in which immune cells infiltrate the exocrine gland. Since SS is caused by a disorder of the immune system, treatments should regulate the immune response. Sphingosylphosphorylcholine (SPC) is a sphingolipid that mediates cellular signaling. In immune cells, SPC has several immunomodulatory functions. Accordingly, this study verifies the immunomodulatory ability and therapeutic effect of SPC in SS. To understand the function of SPC in SS, we treated SPC in female NOD/ShiJcl (NOD) mice. The mice were monitored for 10 weeks, and inflammation in the salivary glands was checked. After SPC treatment, we detected the expression of regulatory B (B

Topics: Animals; B-Lymphocytes, Regulatory; Disease Models, Animal; Female; Humans; Inflammation; Mice; Mice, Inbred NOD; Phosphorylcholine; Sialadenitis; Sjogren's Syndrome; Sphingosine

Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation.

Topics: Biomarkers; Female; Humans; Inflammation; Lipids; Lysophospholipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Phosphorylcholine; Risk Factors; Sphingosine; Tetraspanin 30

Inflammation has an important function in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH); however, the mediators of this inflammatory response have not been clearly identified. In this study, we have investigated the potential function of two sphingolipids, which occur naturally in plasma and serum, sphingosylphosphorylcholine (SPC) and sphingosine 1-phosphate (S1P), to act as proinflammatory mediators in cerebral artery vascular smooth muscle (VSM) cells. In rat cerebral arteries, SPC but not S1P activated p38 mitogen-activated protein kinase (MAPK). Using transcription factor arrays, two proinflammatory transcription factors activated by SPC in cerebral arteries were identified--nuclear factor-κB and CCAAT-enhancer-binding protein. Both these transcription factors were activated by SPC in a p38MAPK-dependent manner. To determine whether this contributed to vascular inflammation, an inflammatory protein array was performed, which showed that SPC increased release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured rat VSM cells. This increase in MCP-1 expression was confirmed in cerebral arteries. The S1P did not increase MCP-1 release. Taken together, our results suggest that SPC, but not S1P, can act as a proinflammatory mediator in cerebral arteries. This may contribute to inflammation observed after SAH and may be part of the initiating event in vasospasm.

Topics: Animals; Blood Platelets; Blotting, Western; Cells, Cultured; Cerebral Arteries; Chemokine CCL2; Electrophoretic Mobility Shift Assay; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Inflammation; Inflammation Mediators; Lysophospholipids; Male; Muscle, Smooth, Vascular; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylcholine; Rats; Rats, Sprague-Dawley; Sphingosine; Subarachnoid Hemorrhage; Transcription Factors; Up-Regulation; Vasospasm, Intracranial

Topics: Animals; Dermatitis; Dose-Response Relationship, Drug; Ear; Histamine; Inflammation; Mast Cells; Mice; Mice, Inbred ICR; Phosphorylcholine; Skin; Sphingosine; Time Factors

Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.

Topics: Antigen Presentation; Antigen-Presenting Cells; Antigens, CD1d; Autoantigens; Cell Line; Cytokines; Humans; Inflammation; Lymphocyte Activation; Lysophosphatidylcholines; Natural Killer T-Cells; Phosphorylcholine; Signal Transduction; Sphingosine