The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat
<p>Abstract</p> <p>Background</p> <p>Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim...
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Format: | Article |
Language: | English |
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BMC
2011-08-01
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Series: | Journal of Neuroinflammation |
Online Access: | http://www.jneuroinflammation.com/content/8/1/107 |
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author | Chen Qing-Wen Kruse Lars S Maddahi Aida Edvinsson Lars |
author_facet | Chen Qing-Wen Kruse Lars S Maddahi Aida Edvinsson Lars |
author_sort | Chen Qing-Wen |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway.</p> <p>Methods</p> <p>The hypothesis was tested <it>in vivo </it>after subarachnoid hemorrhage (SAH) and middle cerebral artery occlusion (MCAO), and <it>in vitro </it>by organ culture of isolated cerebral arteries. The localization and amount of TNF-α, TNF-α receptor 1 and 2 proteins were analysed by immunohistochemistry and western blot after 24 and 48 h of organ culture and at 48 h following SAH or MCAO. In addition, cerebral arteries were incubated for 24 or 48 h in the absence or presence of a B-Raf inhibitor (SB386023-b), a MEK- inhibitor (U0126) or an NF-κB inhibitor (IMD-0354), and protein expression evaluated.</p> <p>Results</p> <p>Immunohistochemistry revealed enhanced expression of TNF-α, TNF-R1 and TNF-R2 in the walls of cerebral arteries at 48 h after MCAO and SAH compared with control. Co-localization studies showed that TNF-α, TNF-R1 and TNF-R2 were primarily localized to the cell membrane and the cytoplasm of the smooth muscle cells (SMC). There was, in addition, some expression of TNF-R2 in the endothelial cells. Immunohistochemistry and western blot analysis showed that these proteins were upregulated after 24 and 48 h in culture, and this upregulation reached an apparent maximum at 48 h of organ culture. Treatment with U0126 significantly reduced the enhanced SMC expression of TNF-α, TNF-R1 and TNF-R2 immunoreactivities after 24 and 48 h of organ culture. The Raf and NF-κB inhibitors significantly reduced organ culture induced TNF-α expression while they had minor effects on the TNF-α receptors.</p> <p>Conclusion</p> <p>The present study shows that cerebral ischemia and organ culture induce expression of TNF-α and its receptors in the walls of cerebral arteries and that upregulation is transcriptionally regulated via the MEK/ERK pathway.</p> |
first_indexed | 2024-12-10T05:15:00Z |
format | Article |
id | doaj.art-1828dd7b3ce349b09dff07b883d5697b |
institution | Directory Open Access Journal |
issn | 1742-2094 |
language | English |
last_indexed | 2024-12-10T05:15:00Z |
publishDate | 2011-08-01 |
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series | Journal of Neuroinflammation |
spelling | doaj.art-1828dd7b3ce349b09dff07b883d5697b2022-12-22T02:00:59ZengBMCJournal of Neuroinflammation1742-20942011-08-018110710.1186/1742-2094-8-107The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in ratChen Qing-WenKruse Lars SMaddahi AidaEdvinsson Lars<p>Abstract</p> <p>Background</p> <p>Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway.</p> <p>Methods</p> <p>The hypothesis was tested <it>in vivo </it>after subarachnoid hemorrhage (SAH) and middle cerebral artery occlusion (MCAO), and <it>in vitro </it>by organ culture of isolated cerebral arteries. The localization and amount of TNF-α, TNF-α receptor 1 and 2 proteins were analysed by immunohistochemistry and western blot after 24 and 48 h of organ culture and at 48 h following SAH or MCAO. In addition, cerebral arteries were incubated for 24 or 48 h in the absence or presence of a B-Raf inhibitor (SB386023-b), a MEK- inhibitor (U0126) or an NF-κB inhibitor (IMD-0354), and protein expression evaluated.</p> <p>Results</p> <p>Immunohistochemistry revealed enhanced expression of TNF-α, TNF-R1 and TNF-R2 in the walls of cerebral arteries at 48 h after MCAO and SAH compared with control. Co-localization studies showed that TNF-α, TNF-R1 and TNF-R2 were primarily localized to the cell membrane and the cytoplasm of the smooth muscle cells (SMC). There was, in addition, some expression of TNF-R2 in the endothelial cells. Immunohistochemistry and western blot analysis showed that these proteins were upregulated after 24 and 48 h in culture, and this upregulation reached an apparent maximum at 48 h of organ culture. Treatment with U0126 significantly reduced the enhanced SMC expression of TNF-α, TNF-R1 and TNF-R2 immunoreactivities after 24 and 48 h of organ culture. The Raf and NF-κB inhibitors significantly reduced organ culture induced TNF-α expression while they had minor effects on the TNF-α receptors.</p> <p>Conclusion</p> <p>The present study shows that cerebral ischemia and organ culture induce expression of TNF-α and its receptors in the walls of cerebral arteries and that upregulation is transcriptionally regulated via the MEK/ERK pathway.</p>http://www.jneuroinflammation.com/content/8/1/107 |
spellingShingle | Chen Qing-Wen Kruse Lars S Maddahi Aida Edvinsson Lars The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat Journal of Neuroinflammation |
title | The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat |
title_full | The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat |
title_fullStr | The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat |
title_full_unstemmed | The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat |
title_short | The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat |
title_sort | role of tumor necrosis factor α and tnf α receptors in cerebral arteries following cerebral ischemia in rat |
url | http://www.jneuroinflammation.com/content/8/1/107 |
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