{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/83668"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/83668","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Regulation of Interleukin -6 Gene Expression in the Brain of Aged Mice","abstract":"The occurrence of certain neurodegenerative diseases increases with age. Because over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative diseases, in the present thesis study the effect of aging on the expression of inflammatory cytokine, interleukin-6 (IL-6), was determined. Competitive RT-PCR and ELISA assay showed that IL-6 mRNA and protein concentration were higher in aged brain compared to adult and neonate brain. To begin identifying the cell type responsible for increased IL-6 in the CNS, glial cells were cultured from brains of neonate, adult, and aged mice. Flow cytometric analysis revealed that increased IL-6 production in glia from aged mice is a result of an increase in reactive microglia, which spontaneously secret copious amount of IL-6. To determine the molecular basis responsible for increased IL-6 gene expression in the aged brain, the binding of transcription factors to the major response elements on the IL-6 promoter was evaluated in brains of 1-, 3-, and 24-month old mice by gel mobility shift assay. Whereas NFkappaB activity was increased in aged brain, NF-IL-6, MRE and AP-1 were either unaffected by aging or decreased. Inhibition of increased NFkappaB activity both in vivo and in vitro decrease IL-6 mRNA expression and protein level. These results suggest that increased NFkappaB activity in aged brain contributes to the elevated levels of IL-6. An anti-inflammatory cytokine IL-10 inhibits NFkappaB activity and expression of IL-6. The coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. Recombinant murine IL-10 decreased NFkappaB DNA binding activity, and therefore, reduced both constitutive and inducible IL-6 mRNA and protein levels in glia from aged mice. However, in glia from adult mice, supplemental IL-10 only decreased inducible, but not constitutive NFkappaB activity, IL-6 mRNA, and IL-6 protein. These data suggest that IL-10 constrains IL-6 gene expression in the adult brain, but in the aged brain it decreases and thus enables a cascade of intracellular events that increase the expression of the IL-6 gene.","abstract_html":"The occurrence of certain neurodegenerative diseases increases with age. Because over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative diseases, in the present thesis study the effect of aging on the expression of inflammatory cytokine, interleukin-6 (IL-6), was determined. Competitive RT-PCR and ELISA assay showed that IL-6 mRNA and protein concentration were higher in aged brain compared to adult and neonate brain. To begin identifying the cell type responsible for increased IL-6 in the CNS, glial cells were cultured from brains of neonate, adult, and aged mice. Flow cytometric analysis revealed that increased IL-6 production in glia from aged mice is a result of an increase in reactive microglia, which spontaneously secret copious amount of IL-6. To determine the molecular basis responsible for increased IL-6 gene expression in the aged brain, the binding of transcription factors to the major response elements on the IL-6 promoter was evaluated in brains of 1-, 3-, and 24-month old mice by gel mobility shift assay. Whereas NFkappaB activity was increased in aged brain, NF-IL-6, MRE and AP-1 were either unaffected by aging or decreased. Inhibition of increased NFkappaB activity both in vivo and in vitro decrease IL-6 mRNA expression and protein level. These results suggest that increased NFkappaB activity in aged brain contributes to the elevated levels of IL-6. An anti-inflammatory cytokine IL-10 inhibits NFkappaB activity and expression of IL-6. The coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. Recombinant murine IL-10 decreased NFkappaB DNA binding activity, and therefore, reduced both constitutive and inducible IL-6 mRNA and protein levels in glia from aged mice. However, in glia from adult mice, supplemental IL-10 only decreased inducible, but not constitutive NFkappaB activity, IL-6 mRNA, and IL-6 protein. These data suggest that IL-10 constrains IL-6 gene expression in the adult brain, but in the aged brain it decreases and thus enables a cascade of intracellular events that increase the expression of the IL-6 gene.","abstract_has_math":false,"creators":["Ye, Shi-Ming"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Animal Sciences","degree_department":null,"school":null,"contributors":["Johnson, Rodney W."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2000,"date_issued":"2000","date_published":"2000","updated_at":"2026-07-22T22:26:21Z","subjects":["Health Sciences, Immunology"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI9990199"],"render_values":[{"text":"(MiAaPQ)AAI9990199","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/83668","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Johnson, Rodney W."]},{"key":"dc:creator","label":"Author","values":["Ye, Shi-Ming"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2000","2015-09-25T21:08:42Z","10000-01-01"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Animal Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health Sciences, Immunology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/83668","(MiAaPQ)AAI9990199"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The occurrence of certain neurodegenerative diseases increases with age. Because over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative diseases, in the present thesis study the effect of aging on the expression of inflammatory cytokine, interleukin-6 (IL-6), was determined. Competitive RT-PCR and ELISA assay showed that IL-6 mRNA and protein concentration were higher in aged brain compared to adult and neonate brain. To begin identifying the cell type responsible for increased IL-6 in the CNS, glial cells were cultured from brains of neonate, adult, and aged mice. Flow cytometric analysis revealed that increased IL-6 production in glia from aged mice is a result of an increase in reactive microglia, which spontaneously secret copious amount of IL-6. To determine the molecular basis responsible for increased IL-6 gene expression in the aged brain, the binding of transcription factors to the major response elements on the IL-6 promoter was evaluated in brains of 1-, 3-, and 24-month old mice by gel mobility shift assay. Whereas NFkappaB activity was increased in aged brain, NF-IL-6, MRE and AP-1 were either unaffected by aging or decreased. Inhibition of increased NFkappaB activity both in vivo and in vitro decrease IL-6 mRNA expression and protein level. These results suggest that increased NFkappaB activity in aged brain contributes to the elevated levels of IL-6. An anti-inflammatory cytokine IL-10 inhibits NFkappaB activity and expression of IL-6. The coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. Recombinant murine IL-10 decreased NFkappaB DNA binding activity, and therefore, reduced both constitutive and inducible IL-6 mRNA and protein levels in glia from aged mice. However, in glia from adult mice, supplemental IL-10 only decreased inducible, but not constitutive NFkappaB activity, IL-6 mRNA, and IL-6 protein. These data suggest that IL-10 constrains IL-6 gene expression in the adult brain, but in the aged brain it decreases and thus enables a cascade of intracellular events that increase the expression of the IL-6 gene.","Made available in DSpace on 2015-09-25T21:08:42Z (GMT). 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Because over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative diseases, in the present thesis study the effect of aging on the expression of inflammatory cytokine, interleukin-6 (IL-6), was determined. Competitive RT-PCR and ELISA assay showed that IL-6 mRNA and protein concentration were higher in aged brain compared to adult and neonate brain. To begin identifying the cell type responsible for increased IL-6 in the CNS, glial cells were cultured from brains of neonate, adult, and aged mice. Flow cytometric analysis revealed that increased IL-6 production in glia from aged mice is a result of an increase in reactive microglia, which spontaneously secret copious amount of IL-6. To determine the molecular basis responsible for increased IL-6 gene expression in the aged brain, the binding of transcription factors to the major response elements on the IL-6 promoter was evaluated in brains of 1-, 3-, and 24-month old mice by gel mobility shift assay. Whereas NFkappaB activity was increased in aged brain, NF-IL-6, MRE and AP-1 were either unaffected by aging or decreased. Inhibition of increased NFkappaB activity both in vivo and in vitro decrease IL-6 mRNA expression and protein level. These results suggest that increased NFkappaB activity in aged brain contributes to the elevated levels of IL-6. An anti-inflammatory cytokine IL-10 inhibits NFkappaB activity and expression of IL-6. The coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. Recombinant murine IL-10 decreased NFkappaB DNA binding activity, and therefore, reduced both constitutive and inducible IL-6 mRNA and protein levels in glia from aged mice. However, in glia from adult mice, supplemental IL-10 only decreased inducible, but not constitutive NFkappaB activity, IL-6 mRNA, and IL-6 protein. These data suggest that IL-10 constrains IL-6 gene expression in the adult brain, but in the aged brain it decreases and thus enables a cascade of intracellular events that increase the expression of the IL-6 gene.","Made available in DSpace on 2015-09-25T21:08:42Z (GMT). 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