Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells
Trying to decrease the production of Amyloid beta (Aβ) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2001-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996101904516 |
| _version_ | 1818414515091406848 |
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| author | Imrich Blasko Alexandra Apochal Guenther Boeck Tobias Hartmann Beatrix Grubeck-Loebenstein Gerhard Ransmayr |
| author_facet | Imrich Blasko Alexandra Apochal Guenther Boeck Tobias Hartmann Beatrix Grubeck-Loebenstein Gerhard Ransmayr |
| author_sort | Imrich Blasko |
| collection | DOAJ |
| description | Trying to decrease the production of Amyloid beta (Aβ) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFα with IFNγ induces the production of Aβ-42 and Aβ-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFα and IFNγ. Ibuprofen treatment decreased the secretion of total Aβ in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Aβ-42 and Aβ-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Aβ by ibuprofen was presumably due to a decreased production of βAPP, which in contrast to the control proteins M2 pyruvate kinase, β-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD. |
| first_indexed | 2024-12-14T11:20:19Z |
| format | Article |
| id | doaj.art-a10bde1a5f8c4f42b55769d00702e0d6 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T11:20:19Z |
| publishDate | 2001-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-a10bde1a5f8c4f42b55769d00702e0d62022-12-21T23:03:47ZengElsevierNeurobiology of Disease1095-953X2001-12-018610941101Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal CellsImrich Blasko0Alexandra Apochal1Guenther Boeck2Tobias Hartmann3Beatrix Grubeck-Loebenstein4Gerhard Ransmayr5Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria; Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biology Heidelberg, University of Heidelberg, Heidelberg, GermanyInstitute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria; Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biology Heidelberg, University of Heidelberg, Heidelberg, GermanyInstitute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria; Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biology Heidelberg, University of Heidelberg, Heidelberg, GermanyInstitute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria; Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biology Heidelberg, University of Heidelberg, Heidelberg, GermanyInstitute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria; Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biology Heidelberg, University of Heidelberg, Heidelberg, GermanyInstitute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria; Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria; Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria; Center for Molecular Biology Heidelberg, University of Heidelberg, Heidelberg, GermanyTrying to decrease the production of Amyloid beta (Aβ) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFα with IFNγ induces the production of Aβ-42 and Aβ-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFα and IFNγ. Ibuprofen treatment decreased the secretion of total Aβ in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Aβ-42 and Aβ-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Aβ by ibuprofen was presumably due to a decreased production of βAPP, which in contrast to the control proteins M2 pyruvate kinase, β-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD.http://www.sciencedirect.com/science/article/pii/S0969996101904516ibuprofenproinflammatory cytokinesamyloid betaBACE-1Alzheimer's disease |
| spellingShingle | Imrich Blasko Alexandra Apochal Guenther Boeck Tobias Hartmann Beatrix Grubeck-Loebenstein Gerhard Ransmayr Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells Neurobiology of Disease ibuprofen proinflammatory cytokines amyloid beta BACE-1 Alzheimer's disease |
| title | Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells |
| title_full | Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells |
| title_fullStr | Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells |
| title_full_unstemmed | Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells |
| title_short | Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells |
| title_sort | ibuprofen decreases cytokine induced amyloid beta production in neuronal cells |
| topic | ibuprofen proinflammatory cytokines amyloid beta BACE-1 Alzheimer's disease |
| url | http://www.sciencedirect.com/science/article/pii/S0969996101904516 |
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