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Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment

Rankine, E.L., Hughes, P.M., Botham, M.S., Perry, V.H. and Felton, L.M. (2006) Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment European Journal of Neuroscience, 24, (1), pp. 77-86. (doi:10.1111/j.1460-9568.2006.04891.x).

Record type: Article

Abstract

We have previously shown that ischaemic lesions are smaller in monocyte chemoattractant protein-1-deficient (MCP-1–/–) mice than in wild-type (wt) controls. In addition to its role as a monocyte chemoattractant, monocyte chemoattractant protein-1 (MCP-1) has been proposed to contribute to lesion progression after focal ischaemia by driving local cytokine synthesis by resident glia. To investigate this hypothesis we injected lipopolysaccharide (LPS) into the brain parenchyma of MCP-1–/– mice and compared the resulting inflammatory response and production of proinflammatory cytokines to those in wt mice. Microglial and astrocyte morphological activation was the same in the two strains, but MCP-1–/– mice showed significantly lower levels of proinflammatory cytokine synthesis; interleukin-1? (IL-1?) and tumour necrosis factor-? (TNF-?) levels were up to 50% lower than in wt controls after 6 h. This reduced synthesis of proinflammatory cytokines occurred well before leucocyte recruitment to the central nervous system (CNS) is observed in this model of acute inflammation and thus cannot be attributed to lower numbers of recruited monocytes at the site of injury. We propose that MCP-1 contributes to acute CNS inflammation by pleiotropic mechanisms. In addition to being a potent chemoattractant for monocytes, we provide evidence here that MCP-1 can modify the responsiveness of CNS glia to acute inflammatory stimuli prior to leucocyte recruitment, thereby acting as a priming stimulus for cytokine synthesis in cells such as microglia.

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Submitted date: 7 February 2006
Published date: 1 July 2006

Identifiers

Local EPrints ID: 56624
URI: http://eprints.soton.ac.uk/id/eprint/56624
ISSN: 0953-816X
PURE UUID: 142d0b10-400e-49ac-8cf3-949dbfe09d5e

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Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:30

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Contributors

Author: E.L. Rankine
Author: P.M. Hughes
Author: M.S. Botham
Author: V.H. Perry
Author: L.M. Felton

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