Transforming growth factor-beta1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix
Transforming growth factor-beta1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix
Previous studies from our laboratory have shown the ME7 model of murine scrapie to be accompanied by an atypical inflammatory response that is characterized by marked astroglial and microglial activation but also by the lack of significant expression of the pro-inflammatory cytokines interleukin (IL)-1? and IL-6. The aim of this study was to determine whether, in the absence of IL-1? and IL-6, tumour necrosis factor (TNF)-? may play an equivalent pro-inflammatory role, or if an anti-inflammatory cytokine profile dominates. We have used competitive polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) to determine the levels of TNF-?, IL-10 and transforming growth factor (TGF)-?1 in the ME7 model, using their expression in lipopolysaccharide (LPS)-induced acute inflammation as a positive control. Levels of mRNA were elevated for all three cytokines during acute inflammation, while TGF-?1 mRNA alone was significantly elevated in ME7-injected brains. Similarly, by ELISA, we detected elevated IL-10, TNF-? and TGF-?1 in LPS-injected animals but only significant elevation of TGF-?1 in ME7-injected animals. An increase in laminin and collagen IV deposition around blood vessels was also observed and is consistent with up-regulation by active TGF-?1. These findings suggest that TGF-?1 may play a central role in maintenance of an atypical microglial phenotype and may also be involved in vascular and extracellular matrix changes
107-119
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
April 2002
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Cunningham, C., Boche, D. and Perry, VH.
(2002)
Transforming growth factor-beta1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix.
Neuropathology and Applied Neurobiology, 28 (2), .
(doi:10.1046/j.1365-2990.2002.00383.x).
Abstract
Previous studies from our laboratory have shown the ME7 model of murine scrapie to be accompanied by an atypical inflammatory response that is characterized by marked astroglial and microglial activation but also by the lack of significant expression of the pro-inflammatory cytokines interleukin (IL)-1? and IL-6. The aim of this study was to determine whether, in the absence of IL-1? and IL-6, tumour necrosis factor (TNF)-? may play an equivalent pro-inflammatory role, or if an anti-inflammatory cytokine profile dominates. We have used competitive polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) to determine the levels of TNF-?, IL-10 and transforming growth factor (TGF)-?1 in the ME7 model, using their expression in lipopolysaccharide (LPS)-induced acute inflammation as a positive control. Levels of mRNA were elevated for all three cytokines during acute inflammation, while TGF-?1 mRNA alone was significantly elevated in ME7-injected brains. Similarly, by ELISA, we detected elevated IL-10, TNF-? and TGF-?1 in LPS-injected animals but only significant elevation of TGF-?1 in ME7-injected animals. An increase in laminin and collagen IV deposition around blood vessels was also observed and is consistent with up-regulation by active TGF-?1. These findings suggest that TGF-?1 may play a central role in maintenance of an atypical microglial phenotype and may also be involved in vascular and extracellular matrix changes
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Published date: April 2002
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Local EPrints ID: 27555
URI: http://eprints.soton.ac.uk/id/eprint/27555
ISSN: 0305-1846
PURE UUID: 72f9f51e-8b0a-49f3-a2a3-0b646da62bf3
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Date deposited: 25 Apr 2006
Last modified: 16 Mar 2024 03:15
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C. Cunningham
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