Expression von TNFa und seinen Rezeptoren p55TNFR und p75TNFR im Gehirn der Maus nach SEB- und LPS-Stimulation
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Philipps-Universität Marburg
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Abstract
Between brain and peripheral immune system exists a bidirectional
communication, which is mediated by soluble factors like cytokines. One of
these proteins is the tumor necrosis factor alpha (TNFa), a proinflammatory
and apoptotic cytokine produced by resident microglia und astrocytes in the
CNS. Both TNF-receptors p55TNFR and p75TNFR are expressed in the brain, thus
TNFa mediated effects in the brain are possible. Nevertheless cells and
mechanisms leading to synthesis of cerebral TNF-receptors are still unknow.
Here, we investigated the cellular distribution of TNFa, p55TNFR and p75TNFR
in normal mouse brain and examined the stimulus-specific effects of
lipopolysacchride (LPS) and staphylococcal enterotoxin B (SEB) at several
time points (1, 4, 8, 12, 24 h p.i.). Both mitogens are known to increase
TNFa serum levels. Different mechanisms of activation of the immune system
represented by these mitogens may enable us to differentiate, if TNFa in
serum itself or in combination with one of the mitogens only is able to
induce TNF-receptor expression in the brain.
In normal mouse brain p55TNFR was expressed in a pan-neuronal manner with
strongest expression in cranial nerv nuclei. Small non-neuronal cells
expressed p75TNFR mRNA all over the brain. LPS als well as SEB stimulated
neuronal activity in the CNS demonstrated by the induction of c-fos mRNA in
the paraventricular nucleus of the hypothalamus (PVN). None of the mitogenes
modulated the constitutive expresssion of p55TNFR mRNA. In contrast,
application of LPS, but not SEB induced TNFa and p75TNFR expression in
circumventricular organs (CVOs).
The comparison of the different effects of LPS and SEB regarding the
TNF-expression pattern in the brain leads us to the conclusion that
immune-to-brain communication is dependent on the mitogen itself. Increased
serum TNF-levels allone are not able to modulate the cerebral TNF-system.
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Dates
Created: 2005Issued: 2005-07-25Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
TNF Receptor p75SEBTNF Receptor p55CytokinesLPSTumor-Nekrose-Faktor RezeptorenZytokineTNF-alpha
DFG-subjects
NeuroimmunologieGehirnTumor-Nekrose-Faktor
DDC-Numbers
610
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Kaut, Oliver (130186287): Expression von TNFa und seinen Rezeptoren p55TNFR und p75TNFR im Gehirn der Maus nach SEB- und LPS-Stimulation. : Philipps-Universität Marburg 2005-07-25. DOI: https://doi.org/10.17192/z2005.0115.
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This item has been published with the following license: In Copyright