Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients
| Autor: | Carla Battisti, Anna Laura Pasqui, Elena Radi, Pietro Enea Lazzerini, Patrizia Formichi, Franco Laghi-Pasini, Anna Di Stefano, Antonio Federico, G. Pompella, Alessandra Leonini |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Lipopolysaccharides Male Programmed cell death Time Factors Physiology medicine.medical_treatment Clinical Biochemistry Apoptosis Enzyme-Linked Immunosorbent Assay Inflammation Biology Peripheral blood mononuclear cell Proinflammatory cytokine medicine Humans Annexin A5 Phytohemagglutinins Cells Cultured Chemokine CCL2 Fluorescent Dyes Electrophoresis Agar Gel Membrane Potential Mitochondrial Tumor Necrosis Factor-alpha Interleukin-8 Psychosine Cell Biology Carbocyanines Flow Cytometry medicine.disease Leukodystrophy Globoid Cell Mitochondria Enzyme Activation Cytokine Microscopy Fluorescence Case-Control Studies Caspases Immunology Leukocytes Mononuclear Krabbe disease Cytokines Benzimidazoles Female Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | Journal of Cellular Physiology. 212:737-743 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | Globoid cell leukodystrophy or Krabbe disease (KD), is a hereditary disorder caused by galactosylceramidase deficiency. Progressive accumulation of psychosine is considered to be the critical pathogenetic mechanism of cell death in the Krabbe brain. Psychosine mechanism of action has not been fully elucidated. It seems to induce apoptosis in oligodendrocytes through a mitochondrial pathway and to up-regulate inflammatory cytokines production resulting in oligodendrocyte loss. Our aim was to evaluate the role of psychosine in apoptotic cell death and inflammatory response in a group of patients affected by KD using peripheral blood lymphocytes (PBLs) and peripheral blood mononuclear cells (PBMCs) as a cellular model. PBLs from KP and healthy controls were exposed to 20 microM psychosine and analysed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy. Our results showed that psychosine induces apoptosis in PBLs through a mitochondrial pathway, but the apoptotic response was quite low especially KP. The role of psychosine in the up-regulation of cytokines (TNFalpha, IL8 and MCP1) has been evaluated by ELISA in PBMCs from KP and controls after stimulation with LPS and phytohemagglutinin. Both in basal condition and after LPS stimulation, cells from KP showed a significant increase in TNF-alpha production, reduced MCP1 levels and no modification in IL8. These results indicate that lymphomonocytes from KP had a basal proinflammatory pattern that was amplified by psychosine. In conclusion, the reduced apoptotic response and the atypical cytokine production observed in our experiments, suggest an involvement of inflammatory pattern in immune peripheral cells of KP. |
| Databáze: | OpenAIRE |
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