Implication of matrix metalloproteinases 2 and 9 in ceramide 1-phosphate-stimulated macrophage migration.

Cell migration is a complex biological function involved in both physiologic and pathologic processes. Although this is a subject of intense investigation, the mechanisms by which cell migration is regulated are not completely understood. In this study we show that the bioactive sphingolipid ceramide 1-phosphate (C1P), which is involved in inflammatory responses, causes upregulation of metalloproteinases (MMP) -2 and -9 in J774A.

Regulation of cell migration and inflammation by ceramide 1-phosphate.

Unlabelled: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid metabolite first shown to regulate cell growth and death. Subsequent studies revealed that C1P was a potent stimulator of cytosolic phospholipase A2 (cPLA2) with ensuing release of arachidonic acid and prostaglandin biosynthesis. The latter findings placed C1P on the list of pro-inflammatory metabolites.

Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells.

Pancreatic cancer is an aggressive and devastating disease characterized by invasiveness, rapid progression and profound resistance to treatment. Despite years of intense investigation, the prognosis of this type of cancer is poor and there is no efficacious treatment to overcome the disease. Using human PANC-1 and MIA PaCa-2 cells, we demonstrate that the bioactive sphingolipid ceramide 1-phosphate (C1P) increases pancreatic cancer cell migration and invasion.

Control of inflammatory responses by ceramide, sphingosine 1-phosphate and ceramide 1-phosphate.

Inflammation is a network of complex processes involving a variety of metabolic and signaling pathways aiming at healing and repairing damage tissue, or fighting infection. However, inflammation can be detrimental when it becomes out of control. Inflammatory mediators involve cytokines, bioactive lipids and lipid-derived metabolites.

Caged ceramide 1-phosphate (C1P) analogs: Novel tools for studying C1P biology.

Ceramide 1-phosphate (C1P) is a bioactive sphingolipid metabolite that is produced in cells by the action of ceramide kinase (CerK) acting upon ceramide, and is also found in the circulation. C1P was first demonstrated to be mitogenic and antiapoptotic in different cell types, and was later shown to induce cell migration. Understanding the precise mechanisms by which C1P exerts its biological effects has been possible using specific photosensitive caged C1P analogues synthesized by Robert Bittman's group.

Sphingomyelinase D/ceramide 1-phosphate in cell survival and inflammation.

Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation.

Phosphatidic acid inhibits ceramide 1-phosphate-stimulated macrophage migration.

Ceramide 1-phosphate (C1P) was recently demonstrated to potently induce cell migration. This action could only be observed when C1P was applied exogenously to cells in culture, and was inhibited by pertussis toxin. However, the mechanisms involved in this process are poorly understood.

Ceramide 1-phosphate induces macrophage chemoattractant protein-1 release: involvement in ceramide 1-phosphate-stimulated cell migration.

The bioactive sphingolipid ceramide 1-phosphate (C1P) is implicated in inflammatory responses and was recently shown to promote cell migration. However, the mechanisms involved in these actions are poorly described. Using J774A.

New insights on the role of ceramide 1-phosphate in inflammation.

Inflammation is a complex biological process involving a variety of locally produced molecules, as well as different types of white blood cells. Some of the so-called inflammatory mediators include cytokines, chemokines, interleukins, prostaglandins, or bioactive lipids, all of which provide protection from infection and foreign substances, such as bacteria, yeast, viruses or some chemicals. Under some circumstances, however, the organism inappropriately activates the immune system triggering an inflammatory response in the absence of foreign insults thereby leading to the establishment of autoimmune diseases.

Ceramide 1-phosphate stimulates glucose uptake in macrophages.

It is well established that ceramide 1-phosphate (C1P) is mitogenic and antiapoptotic, and that it is implicated in the regulation of macrophage migration. These activities require high energy levels to be available in cells. Macrophages obtain most of their energy from glucose.

Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate.

We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P.