MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult
<p>Abstract</p> <p>Background</p> <p>An endotoxin insult mimics a severe peripheral infection and recent evidence suggests that a single exposure can cause long-term cognitive deficits. A peripheral injection of LPS results in production of pro-inflammatory cytokines, s...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-08-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | http://www.jneuroinflammation.com/content/5/1/35 |
| _version_ | 1818807882585473024 |
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| author | Karpus William J Thompson Wendy L Van Eldik Linda J |
| author_facet | Karpus William J Thompson Wendy L Van Eldik Linda J |
| author_sort | Karpus William J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>An endotoxin insult mimics a severe peripheral infection and recent evidence suggests that a single exposure can cause long-term cognitive deficits. A peripheral injection of LPS results in production of pro-inflammatory cytokines, such as IL-1β and TNF-α, in the brain and periphery and these cytokines mediate many effects of the acute phase response including activation of the HPA axis. The chemokine MCP-1 is highly expressed during endotoxemia and although much is known about the importance of MCP-1 in peripheral inflammatory responses to LPS, information about MCP-1 and CNS responses to peripheral LPS is lacking.</p> <p>Methods</p> <p>C57Bl/6 mice were administered LPS by intraperitoneal (i.p.) injection, serum and brains were collected at several time points, and the time course of MCP-1 protein up-regulation was measured. To examine the role of MCP-1 in activation of the brain during acute systemic inflammation, we injected MCP-1 knockout (MCP-1<sup>-/-</sup>) or control C57Bl/6 (MCP-1<sup>+/+</sup>) mice with LPS i.p. and measured the levels of selected cytokines and chemokines in serum and brain extracts 6 hours later. Activated microglia were examined by CD45 immunohistochemistry, and serum corticosterone and ACTH levels were measured by enzyme immunoassay.</p> <p>Results</p> <p>We report that LPS injection induces a robust increase in MCP-1 protein levels in serum and brain, with peak brain levels reached at 6 hrs after LPS administration. MCP-1<sup>-/- </sup>mice injected with LPS showed higher levels of serum IL-1β and TNF-α compared to LPS-treated MCP-1<sup>+/+ </sup>mice. In contrast, these MCP-1<sup>-/- </sup>mice showed significantly lower inductions of brain pro-inflammatory cytokines and chemokines, fewer activated microglia, and a reduction in serum corticosterone levels.</p> <p>Conclusion</p> <p>MCP-1<sup>-/- </sup>mice have decreased brain inflammation after a peripheral LPS insult, despite an exaggerated peripheral response. These data demonstrate an important role for MCP-1 in regulation of brain inflammation after peripheral endotoxemia.</p> |
| first_indexed | 2024-12-18T19:32:44Z |
| format | Article |
| id | doaj.art-e06fc07d1321493cb627a71b5f8e1c66 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-18T19:32:44Z |
| publishDate | 2008-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-e06fc07d1321493cb627a71b5f8e1c662022-12-21T20:55:41ZengBMCJournal of Neuroinflammation1742-20942008-08-01513510.1186/1742-2094-5-35MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insultKarpus William JThompson Wendy LVan Eldik Linda J<p>Abstract</p> <p>Background</p> <p>An endotoxin insult mimics a severe peripheral infection and recent evidence suggests that a single exposure can cause long-term cognitive deficits. A peripheral injection of LPS results in production of pro-inflammatory cytokines, such as IL-1β and TNF-α, in the brain and periphery and these cytokines mediate many effects of the acute phase response including activation of the HPA axis. The chemokine MCP-1 is highly expressed during endotoxemia and although much is known about the importance of MCP-1 in peripheral inflammatory responses to LPS, information about MCP-1 and CNS responses to peripheral LPS is lacking.</p> <p>Methods</p> <p>C57Bl/6 mice were administered LPS by intraperitoneal (i.p.) injection, serum and brains were collected at several time points, and the time course of MCP-1 protein up-regulation was measured. To examine the role of MCP-1 in activation of the brain during acute systemic inflammation, we injected MCP-1 knockout (MCP-1<sup>-/-</sup>) or control C57Bl/6 (MCP-1<sup>+/+</sup>) mice with LPS i.p. and measured the levels of selected cytokines and chemokines in serum and brain extracts 6 hours later. Activated microglia were examined by CD45 immunohistochemistry, and serum corticosterone and ACTH levels were measured by enzyme immunoassay.</p> <p>Results</p> <p>We report that LPS injection induces a robust increase in MCP-1 protein levels in serum and brain, with peak brain levels reached at 6 hrs after LPS administration. MCP-1<sup>-/- </sup>mice injected with LPS showed higher levels of serum IL-1β and TNF-α compared to LPS-treated MCP-1<sup>+/+ </sup>mice. In contrast, these MCP-1<sup>-/- </sup>mice showed significantly lower inductions of brain pro-inflammatory cytokines and chemokines, fewer activated microglia, and a reduction in serum corticosterone levels.</p> <p>Conclusion</p> <p>MCP-1<sup>-/- </sup>mice have decreased brain inflammation after a peripheral LPS insult, despite an exaggerated peripheral response. These data demonstrate an important role for MCP-1 in regulation of brain inflammation after peripheral endotoxemia.</p>http://www.jneuroinflammation.com/content/5/1/35 |
| spellingShingle | Karpus William J Thompson Wendy L Van Eldik Linda J MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult Journal of Neuroinflammation |
| title | MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult |
| title_full | MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult |
| title_fullStr | MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult |
| title_full_unstemmed | MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult |
| title_short | MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult |
| title_sort | mcp 1 deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult |
| url | http://www.jneuroinflammation.com/content/5/1/35 |
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