{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:62170"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:62170","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Regulation of suppressor of cytokine signalling 3 expression by the pro-inflammatory cytokine (IL-1beta) in vitro and inflammatory stimuli in vivo","abstract":"Interleukin-6 (IL-6) exerts pro- as well as anti-inflammatory activities in response to infection, injury or other stimuli which affect the homeostasis of the organism. IL-6-induced expression of acute phase protein genes in the liver is tightly regulated through both IL-6-induced feedback inhibitors and the activity of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. In previous studies mechanisms of how IL-1beta counteracts IL-6-dependent acute phase protein gene induction have been proposed. Apart from negatively regulating the IL-6-type cytokine signalling pathways, SOCS3 is also essential for regulating many immunological processes. In the first part of this thesis, we analyzed how IL-1beta regulates IL-6-induced SOCS3 expression. In hepatocytes IL-1beta alone does not induce SOCS3 expression but it counteracts SOCS3-promoter activation in long term studies (>3h). Surprisingly, short term stimulation (around 50 minutes) revealed IL-1beta to be a potent enhancer of SOCS3 expression in concert with IL-6. This activity of IL-1beta depends neither on IL-1beta-induced p38 MAPKs activity nor on IL-1beta-dependent STAT1-serine phosphorylation, but on NF-kappaB-mediated gene induction. Most importantly, we found IL-6-induced SOCS3 mRNA to be stabilized by the signal propagated from IL-1beta. Such a regulatory network allows IL-1beta to counteract IL-6-dependent expression of acute phase protein genes without inhibiting IL-6-induced SOCS3 expression. Moreover, it provides a sophisticated mechanism for the IL-1beta-dependent inhibition of acute phase protein gene induction since reduced SOCS3 expression would lead to enhanced IL-6 activity.Several signalling pathways have been shown to converge on SOCS3, thereby allowing an extensive cross-talk. However, the individual contribution of each cytokine to the induction of SOCS3 during the inflammatory processes in vivo is not clear. Using IL-6-deficient mice in two well-established animal models of bacterial (LPS) and aseptic (turpentine) inflammation, a central role of IL-6 on hepatic expression of SOCS3 during inflammatory processes was uncovered and is described in the second part of this thesis.","abstract_html":"Interleukin-6 (IL-6) exerts pro- as well as anti-inflammatory activities in response to infection, injury or other stimuli which affect the homeostasis of the organism. IL-6-induced expression of acute phase protein genes in the liver is tightly regulated through both IL-6-induced feedback inhibitors and the activity of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. In previous studies mechanisms of how IL-1beta counteracts IL-6-dependent acute phase protein gene induction have been proposed. Apart from negatively regulating the IL-6-type cytokine signalling pathways, SOCS3 is also essential for regulating many immunological processes. In the first part of this thesis, we analyzed how IL-1beta regulates IL-6-induced SOCS3 expression. In hepatocytes IL-1beta alone does not induce SOCS3 expression but it counteracts SOCS3-promoter activation in long term studies (>3h). Surprisingly, short term stimulation (around 50 minutes) revealed IL-1beta to be a potent enhancer of SOCS3 expression in concert with IL-6. This activity of IL-1beta depends neither on IL-1beta-induced p38 MAPKs activity nor on IL-1beta-dependent STAT1-serine phosphorylation, but on NF-kappaB-mediated gene induction. Most importantly, we found IL-6-induced SOCS3 mRNA to be stabilized by the signal propagated from IL-1beta. Such a regulatory network allows IL-1beta to counteract IL-6-dependent expression of acute phase protein genes without inhibiting IL-6-induced SOCS3 expression. Moreover, it provides a sophisticated mechanism for the IL-1beta-dependent inhibition of acute phase protein gene induction since reduced SOCS3 expression would lead to enhanced IL-6 activity.Several signalling pathways have been shown to converge on SOCS3, thereby allowing an extensive cross-talk. However, the individual contribution of each cytokine to the induction of SOCS3 during the inflammatory processes in vivo is not clear. Using IL-6-deficient mice in two well-established animal models of bacterial (LPS) and aseptic (turpentine) inflammation, a central role of IL-6 on hepatic expression of SOCS3 during inflammatory processes was uncovered and is described in the second part of this thesis.","abstract_has_math":false,"creators":["Yang, Xiangping"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Heinrich, Peter C."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2005,"date_issued":"2005","date_published":"2005","updated_at":"2026-07-30T19:43:19Z","subjects":["info:eu-repo/classification/ddc/610","Medizin","Interleukin","SOCS","Entzündung","Genexpression","inflammation","gene expression"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123760%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123760%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123760%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/62170","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Heinrich, Peter C."]},{"key":"dc:creator","label":"Author","values":["Yang, Xiangping"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2005"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-12718"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Medizin","Interleukin","SOCS","Entzündung","Genexpression","inflammation","gene expression"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/62170","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123760%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Interleukin-6 (IL-6) exerts pro- as well as anti-inflammatory activities in response to infection, injury or other stimuli which affect the homeostasis of the organism. IL-6-induced expression of acute phase protein genes in the liver is tightly regulated through both IL-6-induced feedback inhibitors and the activity of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. In previous studies mechanisms of how IL-1beta counteracts IL-6-dependent acute phase protein gene induction have been proposed. Apart from negatively regulating the IL-6-type cytokine signalling pathways, SOCS3 is also essential for regulating many immunological processes. In the first part of this thesis, we analyzed how IL-1beta regulates IL-6-induced SOCS3 expression. In hepatocytes IL-1beta alone does not induce SOCS3 expression but it counteracts SOCS3-promoter activation in long term studies (>3h). Surprisingly, short term stimulation (around 50 minutes) revealed IL-1beta to be a potent enhancer of SOCS3 expression in concert with IL-6. This activity of IL-1beta depends neither on IL-1beta-induced p38 MAPKs activity nor on IL-1beta-dependent STAT1-serine phosphorylation, but on NF-kappaB-mediated gene induction. Most importantly, we found IL-6-induced SOCS3 mRNA to be stabilized by the signal propagated from IL-1beta. Such a regulatory network allows IL-1beta to counteract IL-6-dependent expression of acute phase protein genes without inhibiting IL-6-induced SOCS3 expression. Moreover, it provides a sophisticated mechanism for the IL-1beta-dependent inhibition of acute phase protein gene induction since reduced SOCS3 expression would lead to enhanced IL-6 activity.Several signalling pathways have been shown to converge on SOCS3, thereby allowing an extensive cross-talk. However, the individual contribution of each cytokine to the induction of SOCS3 during the inflammatory processes in vivo is not clear. Using IL-6-deficient mice in two well-established animal models of bacterial (LPS) and aseptic (turpentine) inflammation, a central role of IL-6 on hepatic expression of SOCS3 during inflammatory processes was uncovered and is described in the second part of this thesis."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University 93 S. : graph. Darst. (2005). = Aachen, Techn. Hochsch., Diss., 2005"]},{"key":"dc:title","label":"Title","values":["Regulation of suppressor of cytokine signalling 3 expression by the pro-inflammatory cytokine (IL-1beta) in vitro and inflammatory stimuli in vivo"]}]}],"canonical_facts":{"dc:contributor":["Heinrich, Peter C."],"dc:coverage":["DE"],"dc:creator":["Yang, Xiangping"],"dc:date":["2005"],"dc:description":["Interleukin-6 (IL-6) exerts pro- as well as anti-inflammatory activities in response to infection, injury or other stimuli which affect the homeostasis of the organism. IL-6-induced expression of acute phase protein genes in the liver is tightly regulated through both IL-6-induced feedback inhibitors and the activity of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. In previous studies mechanisms of how IL-1beta counteracts IL-6-dependent acute phase protein gene induction have been proposed. Apart from negatively regulating the IL-6-type cytokine signalling pathways, SOCS3 is also essential for regulating many immunological processes. In the first part of this thesis, we analyzed how IL-1beta regulates IL-6-induced SOCS3 expression. In hepatocytes IL-1beta alone does not induce SOCS3 expression but it counteracts SOCS3-promoter activation in long term studies (>3h). Surprisingly, short term stimulation (around 50 minutes) revealed IL-1beta to be a potent enhancer of SOCS3 expression in concert with IL-6. This activity of IL-1beta depends neither on IL-1beta-induced p38 MAPKs activity nor on IL-1beta-dependent STAT1-serine phosphorylation, but on NF-kappaB-mediated gene induction. Most importantly, we found IL-6-induced SOCS3 mRNA to be stabilized by the signal propagated from IL-1beta. Such a regulatory network allows IL-1beta to counteract IL-6-dependent expression of acute phase protein genes without inhibiting IL-6-induced SOCS3 expression. Moreover, it provides a sophisticated mechanism for the IL-1beta-dependent inhibition of acute phase protein gene induction since reduced SOCS3 expression would lead to enhanced IL-6 activity.Several signalling pathways have been shown to converge on SOCS3, thereby allowing an extensive cross-talk. However, the individual contribution of each cytokine to the induction of SOCS3 during the inflammatory processes in vivo is not clear. Using IL-6-deficient mice in two well-established animal models of bacterial (LPS) and aseptic (turpentine) inflammation, a central role of IL-6 on hepatic expression of SOCS3 during inflammatory processes was uncovered and is described in the second part of this thesis."],"dc:identifier":["https://publications.rwth-aachen.de/record/62170","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123760%22"],"dc:language":["eng"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-12718"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University 93 S. : graph. Darst. (2005). = Aachen, Techn. Hochsch., Diss., 2005"],"dc:subject":["info:eu-repo/classification/ddc/610","Medizin","Interleukin","SOCS","Entzündung","Genexpression","inflammation","gene expression"],"dc:title":["Regulation of suppressor of cytokine signalling 3 expression by the pro-inflammatory cytokine (IL-1beta) in vitro and inflammatory stimuli in vivo"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:43:19Z"}