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.
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)
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Translated abstract: |
Abstract | Language |
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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 |
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Creators: |
Creators | Email | ORCID | ORCID Put Code |
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Thom, Felicitas | Felicitas.Thom@cecete.de | UNSPECIFIED | UNSPECIFIED |
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URN: |
urn:nbn:de:hbz:38-15884 |
Date: |
2005 |
Language: |
German |
Faculty: |
Faculty of Mathematics and Natural Sciences |
Divisions: |
Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry |
Subjects: |
Life sciences |
Uncontrolled Keywords: |
Keywords | Language |
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LPS, Monozyten, Interleukine | German | LPS, monocytes, interleucine | English |
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Date of oral exam: |
7 July 2005 |
Referee: |
Name | Academic Title |
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Klein, Helmuth W.( Prof. Dr.) | UNSPECIFIED |
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Refereed: |
Yes |
URI: |
http://kups.ub.uni-koeln.de/id/eprint/1588 |
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