Role of alpha-metylacyl-CoA racemase in immune cells during the development of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and alteration of the metabolism of immune cells is an attractive strategy to modify their function during autoimmunity in MS. We investigated the effect of modulating fatty acid metabolism in an animal model of multiple sclerosis, myelin oligodendrocyte glycoprotein (MOG)35–55-induced, chronic progressive, experimental autoimmune encephalomyelitis (EAE) in C57/BL6 mice. Alpha-methylacyl-CoA racemase (AMACR) converts R-configurated branched fatty acids to the S-configuration, thereby preparing them for metabolic β-oxidation. We observed significant, selective, disease-dependent elevation of AMACR expression in various immune cells (monocytes/B cells/T cells) isolated from blood, draining lymph nodes and spleen in EAE mice during the preclinical phase. In vitro studies revealed that genetic deletion of AMACR inhibits the proliferation of T cells. However, AMACR−/− mice showed only a slight worsening of early (days 12–14) clinical symptoms of EAE and no alteration in cognitive behavior in comparison to wild type mice. This was accompanied over the same period by an increased number of neutrophils in the blood and of B cells and T cells in the lymph nodes of AMACR−/− EAE mice in comparison to wild-type EAE mice. In conclusion, our data suggest that AMACR is regulated in immune cells during EAE but it is not essential for the development of EAE

Induction of experimental autoimmune encephalomyelitis in mice and evaluation of the disease-dependent distribution of immune cells in various tissues

Multiple sclerosis is presumed to be an inflammatory autoimmune disease, which is characterized by lesion formation in the central nervous system (CNS) resulting in cognitive and motor impairment. Experimental autoimmune encephalomyelitis (EAE) is a useful animal model of MS, because it is also characterized by lesion formation in the CNS, motor impairment and is also driven by autoimmune and inflammatory reactions. One of the EAE models is induced with a peptide derived from the myelin oligodendrocyte protein (MOG)35-55 in mice. The EAE mice develop a progressive disease course. This course is divided into three phases: the preclinical phase (day 0 - 9), the disease onset (day 10 - 11) and the acute phase (day 12 - 14). MS and EAE are induced by autoreactive T cells that infiltrate the CNS. These T cells secrete chemokines and cytokines which lead to the recruitment of further immune cells. Therefore, the immune cell distribution in the spinal cord during the three disease phases was investigated

Regulation of ceramide synthase 6 in a spontaneous experimental autoimmune encephalomyelitis model is sex dependent

Ceramides (Cer) are mediators of inflammatory processes. In a chronic experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), we observed a significant elevation of C16-Cer and its synthesizing enzyme, ceramide synthase(CerS)6, in the lumbar spinal cord. In the present study, we have confirmed that C16-Cer and CerS6 are also upregulated in the lumbar spinal cord in a spontaneous relapse-remitting EAE model, using SJL mice overexpressing a transgenic T cell receptor (TCR1640). CerS6 was found to be expressed in macrophages, T cells and B cells in EAE lesions. In macrophages, we demonstrated that interferon gamma (IFN-gamma)-induced CerS6 upregulation was amplified by 17 beta-estradiol, an action that was further accompanied by increased upregulation of tumor necrosis factor alpha (TNF-alpha). Accordingly, CerS6 and TNF-alpha expression was upregulated predominantly in the spinal cord in female TCR1640 mice, which usually develop the relapse-remitting form of EAE, while male TCR1640 mice showed an attenuated regulation of CerS6. and TNF-alpha and exhibit mostly chronic disease progression. Furthermore, expression of TNFR2, one of two receptors of TNF-alpha, which is linked to neuroprotection and remyelination, was also upregulated to a greater extent during EAE in female TCR1640 mice in comparison to male TCR1640 mice. Taken together, our results confirm the upregulation of CerS6 and C16-Cer in an adjuvant-independent, physiological EAE model and further suggest an anti-inflammatory role of CerS6 in the regulation of the disease course in female TCR1640 mice via TNF-alpha/TNFR2. (C) 2014 Elsevier Inc. All rights reserved

Zastosowanie infrastruktury gridowej do badań hydrometeorologicznych

The Distributed Research Infrastructure for Hydro-Meteorological Study (DRIHMS) is a co-ordinated action co-funded by the European Commission. DRIHMS analyzes the main issues that arise when designing and setting up a pan-European Grid-based e-Infrastructure for research activities in the hydrologic and meteorological fields. The main outcome of the project is represented first by a set of Grid usage patterns to support innovative hydro-meteorological research activities, and second by the implications that such patterns define for a dedicated Grid infrastructure and the respective Grid architecture.Rozproszona infrastruktura naukowa przeznaczona do badań hydrometeorologicznych (Distributed Research Infrastructure for Hydro-Meteorological Study - DRIHMS) stanowi element skoordynowanej akcji współfinansowanej przez Komisję Europejską. Celem DRIHMS jest analiza głównych problemów spotykanych w dziedzinie hydrologii i meteorologii. Głównym wynikiem projektu będzie zestaw wzorców użytkowania środowisk gridowych w celu wspomagania nowoczesnych badań hydrometeorologicznych oraz wnioski wynikające z powyższego zastosowania, mogące mieć wpływ na dalszy rozwój dedykowanych rozwiązań gridowych