Nuclear Translocation of SGPP-1 and Decrease of SGPL-1 Activity Contribute to Sphingolipid Rheostat Regulation of Inflammatory Dendritic Cells
نویسندگان
چکیده
A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
منابع مشابه
Effect of Ovarian Induction Using PMSG and HCG hormones on Uterus Dendritic Cells Population in NMRI mice
Introduction: Ovarian hyper-stimulation is widely used in IVF clinics. The main purpose of this method is to stimulate folliculogenesis and increase the number of oocytes in one cycle. Following ovarian hyper-stimulation, hormonal secretion of the ovary, particularly estradiol and progesterone dramatically increases. Immune cells especially dendritic cells have receptors for the estradiol...
متن کاملP 141: Mesenchymal Stem Cells as Treatment in Neuroinflammatory Disease
Mesenchymal stem cells can be obtained from deferent tissues like adipose tissue, umbilical cord, placenta, skin, bone marrow, etc. These cells have regulatory effects on all types of immune cells such as dendritic cell, natural killers and lymphocytes. Mesenchymal stem cells induce inhibitory phenotypes of Antigen Presenting Cells (APCs) following their activity. They also change T cells pheno...
متن کاملDoes Nitric Oxide Generated by Dendritic Cells Contribute to the Low Incidence of GVHD after Cord Blood Transplantation?
متن کامل
IMMUNOBIOLOGY HIV-1 infection of human macrophages directly induces viperin which inhibits viral production
Macrophages are key target cells for HIV-1. HIV-1BaL induced a subset of interferonstimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, ...
متن کاملThe protein kinase Sch 9 is a key regulator
The Saccharomyces cerevisiae protein kinase Sch9 has been demonstrated to be an in vitro and in vivo effector of sphingolipid signalling. In this study, the link between Sch9 and sphingolipid metabolism in S. cerevisiae was examined in vivo based on the observation that the sch9Δ mutant displays altered sensitivities to various inhibitors of sphingolipid metabolism, i.e. myriocin and aureobasid...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 2017 شماره
صفحات -
تاریخ انتشار 2017