Expression von TNFa und seinen Rezeptoren p55TNFR und p75TNFR im Gehirn der Maus nach SEB- und LPS-Stimulation

Zwischen Gehirn und peripherem Immunsystem besteht eine bidirektionale Kommunikation, die u.a. durch lösliche Faktoren wie Zytokine mediiert wird. Eines der dabei beteiligten Proteine ist der Tumor-Nekrose-Faktor-alpha (TNFa), ein proinflammatorisch und apoptotisch wirkendes Zytokin, das im ZNS von...

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Bibliographic Details
Main Author: Kaut, Oliver
Contributors: Weihe, Eberhard (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2005
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Table of Contents: 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.