{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:59208"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:59208","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Vergleich der Signaltransduktion von Interleukin-6 und Interleukin-10 in primären humanen Makrophagen","abstract":"Different sensitivities of IL-10- and IL-6-induced STAT3 activation towards inhibitory mechanisms in primary human macrophages. Interleukin-10 (IL-10) acts on human macrophages as a more potent anti-inflammatory cytokine than interleukin-6 (IL-6) although both cytokines signal mainly via activation of the transcription factor STAT3. In this study I compared IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Whereas pretreatment of macrophages with PMA or the pro-inflammatory mediators LPS and TNFalpha blocks IL-6-induced STAT3 activation, IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor SOCS3 in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not dependent on gene transcription. Pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6 whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling towards the feedback inhibitor SOCS3 that is induced by both cytokines. Whereas the IL-6 signal transducer gp130 has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), sequence comparison of phosphotyrosine motifs suggests that the SH2-domain of SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling towards mechanisms that inhibit the Jak/STAT pathway define an important mechanism that contributes to the different anti-inflammatory potencies of these two cytokines.","abstract_html":"Different sensitivities of IL-10- and IL-6-induced STAT3 activation towards inhibitory mechanisms in primary human macrophages. Interleukin-10 (IL-10) acts on human macrophages as a more potent anti-inflammatory cytokine than interleukin-6 (IL-6) although both cytokines signal mainly via activation of the transcription factor STAT3. In this study I compared IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Whereas pretreatment of macrophages with PMA or the pro-inflammatory mediators LPS and TNFalpha blocks IL-6-induced STAT3 activation, IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor SOCS3 in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not dependent on gene transcription. Pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6 whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling towards the feedback inhibitor SOCS3 that is induced by both cytokines. Whereas the IL-6 signal transducer gp130 has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), sequence comparison of phosphotyrosine motifs suggests that the SH2-domain of SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling towards mechanisms that inhibit the Jak/STAT pathway define an important mechanism that contributes to the different anti-inflammatory potencies of these two cytokines.","abstract_has_math":false,"creators":["Niemand, Claudia"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Heinrich, P. 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Interleukin-10 (IL-10) acts on human macrophages as a more potent anti-inflammatory cytokine than interleukin-6 (IL-6) although both cytokines signal mainly via activation of the transcription factor STAT3. In this study I compared IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Whereas pretreatment of macrophages with PMA or the pro-inflammatory mediators LPS and TNFalpha blocks IL-6-induced STAT3 activation, IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor SOCS3 in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not dependent on gene transcription. Pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6 whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling towards the feedback inhibitor SOCS3 that is induced by both cytokines. Whereas the IL-6 signal transducer gp130 has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), sequence comparison of phosphotyrosine motifs suggests that the SH2-domain of SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling towards mechanisms that inhibit the Jak/STAT pathway define an important mechanism that contributes to the different anti-inflammatory potencies of these two cytokines."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University V, 78 S : Ill., graph. Darst. (2002). = Aachen, Techn. Hochsch., Diss., 2002"]},{"key":"dc:title","label":"Title","values":["Vergleich der Signaltransduktion von Interleukin-6 und Interleukin-10 in primären humanen Makrophagen"]}]}],"canonical_facts":{"dc:contributor":["Heinrich, P. C."],"dc:coverage":["DE"],"dc:creator":["Niemand, Claudia"],"dc:date":["2002"],"dc:description":["Different sensitivities of IL-10- and IL-6-induced STAT3 activation towards inhibitory mechanisms in primary human macrophages. Interleukin-10 (IL-10) acts on human macrophages as a more potent anti-inflammatory cytokine than interleukin-6 (IL-6) although both cytokines signal mainly via activation of the transcription factor STAT3. In this study I compared IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Whereas pretreatment of macrophages with PMA or the pro-inflammatory mediators LPS and TNFalpha blocks IL-6-induced STAT3 activation, IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor SOCS3 in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not dependent on gene transcription. Pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6 whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling towards the feedback inhibitor SOCS3 that is induced by both cytokines. Whereas the IL-6 signal transducer gp130 has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), sequence comparison of phosphotyrosine motifs suggests that the SH2-domain of SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling towards mechanisms that inhibit the Jak/STAT pathway define an important mechanism that contributes to the different anti-inflammatory potencies of these two cytokines."],"dc:identifier":["https://publications.rwth-aachen.de/record/59208","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121015%22"],"dc:language":["ger"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-4296"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University V, 78 S : Ill., graph. Darst. (2002). = Aachen, Techn. Hochsch., Diss., 2002"],"dc:subject":["info:eu-repo/classification/ddc/610","Medizin"],"dc:title":["Vergleich der Signaltransduktion von Interleukin-6 und Interleukin-10 in primären humanen Makrophagen"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:42:39Z"}