Thom, Felicitas (2005). Wirkungen von Aminothalidomid und Suramin auf die LPS-induzierte Zytokinbildung von TNFá, IL-12p40 und IL-10 in CD-14+-Monozyten. PhD thesis, Universität zu Köln.

[img]
Preview
PDF
Diss_ThomF_2005.pdf

Download (4MB)

Abstract

Ein Ansatz zur Therapie von Autoimmunerkrankungen liegt in der Beeinflussung der fehlregulierten Zytokinbildung von Immunzellen. In der vorliegenden Arbeit wurde die Regulation der Bildung der pro-entzuendlichen Zytokine TNFá und IL-12(p40) sowie des anti-entzuendlichen Zytokins IL-10 im Modell der LPS-stimulierten CD-14+-Monozyten durch Aminothalidomid und Suramin untersucht. In LPS-stimulierten CD-14+-Monozyten verringerte Aminothalidomid die TNFá- und IL-12(p40)-Bildung fast vollstaendig, waehrend die IL-10-Bildung gesteigert wurde (mRNA- und Protein-Ebene). Aminothalidomid veraenderte die IL?12(p40)- bzw. IL-10-Bildung aufgrund einer veraenderten Zahl an sezernierenden CD-14+-Monozyten. Die Wirkung von Aminothalidomid auf die IL-12(p40)-Bildung erfolgte unabhaengig von der gleichzeitigen Steigerung der IL-10-Bildung und wurde nicht ueber die bekannte, hemmende Wirkung des IL-10-Proteins auf die IL-12-Bildung vermittelt. Suramin fuehrte zur Inaktivierung von biologisch aktivem IL-10-Protein, wodurch die hemmende Wirkung des IL-10-Proteins auf die TNFá- und IL-12-Bildung verhindert wurde. Dies fuehrte zu einer gesteigerten TNFá- und IL-12(p40)-Bildung (mRNA- und Protein-Ebene).

Item Type: Thesis (PhD thesis)
Translated abstract:
AbstractLanguage
In many autoimmune diseases, a dysregulation of the production of the pro- and anti-inflammatory cytokines such as TNFá and IL-12 and the anti-inflammatory cytokine IL-10 has been observed. One possible approach to treating such diseases would be using immune-modulatory substances that change the rate of the production of these pro- and anti-inflammatory cytokines. The effect of 4-amino-thalidomide and suramine on the LPS-stimulated cytokine production of TNFá, IL-12 and IL-10 has been studied in CD-14+-monocytes. 4-amino-thalidomide decreased the production of TNFá, IL 12(p40) and raised the secretion of IL-10 in LPS-stimulated CD-14+-monocytes (on both mRNA and protein level). Staining of individual LPS-activated CD-14+-monocytes showed that most of the cells were IL-12-positve in the absence of 4-amino-thalidomide whereas only a few cells showed a weak signal in its presence. In contrast, the vast majority of LPS-activated CD-14+-monocytes had a strong staining for IL-10 in the presence of 4-amino-thalidomide. Time course analysis demonstrated that in the presence of 4-amino-thalidomide the IL-10-protein could be detected earlier than in the LPS-control group and higher amounts of IL-10 were measured in the supernatant. All in all, the experiments described here demonstrate the 4-amino-thalidomide modulates TLR4-signaling by LPS-activated CD-14+-monocytes, resulting in strong inhibition of TNFá, IL-12p40, and a pronounced upregulation of IL-10 synthesis at the protein as well as mRNA level and that both effects are regulated independently by 4-amino-thalidomide. Suramine inactivated the biological activity of human IL-10 Protein. Therefore, no feedback-repression on the production of IL 12(p40) and TNFá occurred, resulting in an increased TNFá- and IL-12(p40)-production (on both mRNA and protein level). The 10-production (mRNA and protein) in LPS-stimulated CD-14+-monocytes was not affected by suramine. English
Creators:
CreatorsEmailORCID
Thom, FelicitasFelicitas.Thom@cecete.deUNSPECIFIED
URN: urn:nbn:de:hbz:38-15884
Subjects: Life sciences
Uncontrolled Keywords:
KeywordsLanguage
LPS, Monozyten, InterleukineGerman
LPS, monocytes, interleucineEnglish
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Institute for Biochmemistry
Language: German
Date: 2005
Date of oral exam: 7 July 2005
Referee:
NameAcademic Title
Klein, Helmuth W.( Prof. Dr.)UNSPECIFIED
Full Text Status: Public
Date Deposited: 15 Dec 2005 11:02
URI: http://kups.ub.uni-koeln.de/id/eprint/1588

Downloads

Downloads per month over past year

Export

Actions (login required)

View Item View Item