Publikationsserver der RWTH Aachen University
Chemokinaktivität induziert durch Interleukin-6
Abstract
dc:descriptionInterleukin-6 belongs to the IL-6 type cytokine family. It signals through a receptor complex composed of the IL-6Ralpha and the signal-transducing subunit gp130. The activation of this receptor complex leads to the activation of the JAK/STAT pathway, the MAPK- and PI3K-caskade. IL-6 plays an important role in the induction of acut-phase proteins. Migration is most importantly induced by chemokines, which signal through G-protein coupled receptors. Only a few cytokines, signalling via receptor-tyrosin-kinases or via receptors associated with kinases, had been shown to induce cell migration. In a previous publication we could demonstrate for the first time, that IL-6 induces directly chemotactic migration of T-cells. In the study presented here the biological properties of IL-6 which are crucial for the migration of monocytes have been analyzed in detail. The first crucial step for leukocyte recruitment is the activation of integrins. Here it is shown that IL-6-induces activation of beta1-integrin on both, TUR-cells and RAW 264.7-cells as well as on primary human CD14+-monocytes. The second stimulation-dependent step is the adhesion of leukocytes to endothelial cells. Using cell adhesion assays it could be demonstrate that IL-6 treated TUR-cells adhere to endothelial cells as efficient as SDF-1-treated cells. For subsequent cell migration actin polymerization at the leading edge is important. Indeed, stimulation with IL-6 induces the actin polymerization in both, TUR-monocytic cells and RAW 264.7 macrophages as well as in primary human CD14+-monocytes. In addition, IL-6 induces fibronectin-dependent migration and transmigration through a layer of endothelial-cells. Furthermore, it was analyzed whether the transcription factor STAT3 is involved in IL-6-induced cell migration. Here, it could be demonstrated that the STAT3-inhibitor Galiellalacton reduces the IL-6-induced fibronectin-dependent migration of TUR-cells. However the previously described inhibition of STAT3 DNA-binding could not be confirmed in this study. FAK plays an important role in migration. For only a few receptor-tyrosine kinases direct binding of FAK to the receptor could be demonstrated. In the thesis presented here it has been shown for the first time that FAK binds to the gp130 receptor subunit of the IL-6 receptor complex. IL-6 fulfills all biological properties of a chemotactic cytokine even though, and in contrast to classical chemokines, IL-6 does not signal through G-protein coupled receptors.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2009
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
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- Clahsen, Thomas
- Contributors dc:contributor
-
- Schaper, Fred
Subjects
dc:subject × 4Rights
dc:rights- Statement dc:rights
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- info:eu-repo/semantics/openAccess
- Language dc:language
- ger