Programmed cell death is vital for a number of pathophysiologic settings. Apoptotic cells are rapidly engulfed by phagocytes (ie, macrophages), which in turn acquire an anti-inflammatory phenotype known as alternative activation or the M2-type. Here we show that interaction of apoptotic cells with macrophages attenuates cell death pathways in the latter. Protection of human macrophages required...

Sphingosine-1-phosphate (S1P) is a plasma lipid mediator with multiple roles in mammalian development, physiology and pathophysiology. It is constitutively produced mostly by erythrocytes by the action of sphingosine kinase 1 (SphK1), resulting in high (∼0.5 micromolar) steady-state plasma S1P content and steep S1P concentration gradient imposed between plasma/lymph/tissue interstitial fluid. S...

Sphingosine kinase (Sphk) has been shown to be activated by growth factor and survival factors, and one of its products, sphingosine-1-phosphate, plays an important role in the regulation of various cellular responses. However, the effect of Sphk on the maturation and immunostimulatory function of dendritic cells (DCs) still remains largely unknown. In this study, we examined whether sphingosin...

This paper explores the way ceramide, sphingosine, ceramide 1-phosphate, and sphingosine 1-phosphate modulate the generation of second lipid messengers from phosphatidic acid in two experimental models of the central nervous system: in vertebrate rod outer segments prepared from dark-adapted retinas as well as in rod outer segments prepared from light-adapted retinas and in rat cerebral cortex ...

BACKGROUND AND PURPOSE Isoflurane, administered before or during cerebral ischemia, has been shown to exhibit neuroprotection in animal models of ischemic stroke. However, the underlying mechanism remains to be elucidated. In the present study, we determined whether isoflurane posttreatment provides neuroprotection after neonatal hypoxia-ischemia (HI) in rats and evaluated the role of the sphin...

Sphingosine kinase (SphK) 1 and 2 phosphorylate sphingosine to generate sphingosine-1-phosphate (S1P), a pluripotent lipophilic mediator implicated in a variety of cellular events. Here we show that the activity of β-site APP cleaving enzyme-1 (BACE1), the rate-limiting enzyme for amyloid-β peptide (Aβ) production, is modulated by S1P in mouse neurons. Treatment by SphK inhibitor, RNA interfere...

Immunotherapeutic drugs that mimic sphingosine 1-phosphate (S1P) disrupt lymphocyte trafficking and cause T helper and T effector cells to be retained in secondary lymphoid tissue and away from sites of inflammation. The prototypical therapeutic agent, 2-alkyl-2-amino-1,3-propanediol (FTY720), stimulates S1P signaling pathways only after it is phosphorylated by one or more unknown kinases. We g...

Increasing evidence suggests that sphingosine-1-phosphate (S1P) is involved in the pathogenesis of allergic bronchial asthma. In the present study, the changes in the expression levels of enzymes associated with S1P turnover were determined in a mouse model of allergic bronchial asthma. Male BALB/c mice were actively sensitized with ovalbumin antigen, and were repeatedly challenged with aerosol...

High plasma levels of the sphingolipid intermediates ceramide (Cer) and sphingosine-1-phosphate (S1P) are suggested to be involved in development insulin resistance (IR). Recent evidence indicates that advanced glycation endproducts (AGEs) can alter sphingolipids metabolism equilibrium. Since enzymes responsible for rheostat maintenance highly expressed liver, we thus investigated whether AGEs ...

Early growth and differentiation of the pancreatic endoderm is regulated by soluble factors from the pancreatic mesenchyme. Previously, we demonstrated that N-cadherin-deficient mice lack a dorsal pancreas, due to a critical role of N-cadherin in dorsal pancreatic mesenchymal cell survival. Here, we show that restoring cardiac and circulatory function in N-cadherin null mice by cardiac-specific...