Makwana, M;
Jones, LL;
Cuthill, D;
Heuer, H;
Bohatschek, M;
Hristova, M;
Friedrichsen, S;
... Raivich, G; + view all
(2007)
Endogenous TGF-beta 1 suppresses inflammation and promotes survival in adult CNJS.
Journal of Neuroscience
, 27
(42)
pp. 11201-11213.
10.1523/JNEUROSCI.2255-07.2007.
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Abstract
Transforming growth factor β1 (TGFβ1) is a pleiotropic cytokine with potent neurotrophic and immunosuppressive properties that is upregulated after injury, but also expressed in the normal nervous system. In the current study, we examined the regulation of TGFβ1 and the effects of TGFβ1 deletion on cellular response in the uninjured adult brain and in the injured and regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks after birth in TGFβ1-deficient mice, this study was performed on a T- and B-cell-deficient RAG2−/− background. Compared with wild-type siblings, homozygous deletion of TGFβ1 resulted in an extensive inflammatory response in otherwise uninjured brain parenchyma. Astrocytes increased in GFAP and CD44 immunoreactivity; microglia showed proliferative activity, expression of phagocytosis-associated markers [αXβ2, B7.2, and MHC1 (major histocompatibility complex type 1)], and reduced branching. Ultrastructural analysis revealed focal blockade of axonal transport, perinodal damming of axonal organelles, focal demyelination, and myelin debris in granule-rich, phagocytic microglia. After facial axotomy, absence of TGFβ1 led to a fourfold increase in neuronal cell death (52 vs 13%), decreased central axonal sprouting, and significant delay in functional recovery. It also interfered with the microglial response, resulting in a diminished expression of early activation markers [ICAM1 (intercellular adhesion molecule 1), α6β1, and αMβ2] and reduced proliferation. In line with axonal and glial findings in the otherwise uninjured CNS, absence of endogenous TGFβ1 also caused an ∼10% reduction in the number of normal motoneurons, pointing to an ongoing and potent trophic role of this anti-inflammatory cytokine in the normal as well as in the injured brain.
| Type: | Article |
|---|---|
| Title: | Endogenous TGF-beta 1 suppresses inflammation and promotes survival in adult CNJS |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/JNEUROSCI.2255-07.2007 |
| Publisher version: | http://dx.doi.org/10.1523/JNEUROSCI.2255-07.2007 |
| Language: | English |
| Additional information: | This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. |
| Keywords: | 1, inflammation, AND, SURVIVAL, Adult |
| URI: | https://discovery.ucl.ac.uk/id/eprint/126525 |
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