C-reactive protein (CRP) is an acute phase protein produced by hepatocytes whose serum concentration increases in inflammatory conditions including cardiovascular complications. Statins that are used in the treatment of cardiovascular diseases to reduce cholesterol also lower serum CRP levels. In human hepatoma Hep3B cells, CRP is induced in response to cytokines IL-6 and IL-1β. The objective of the study was to determine the mechanism of regulation of CRP gene expression in Hep3B cells in response to cytokines and to determine the effect of statins on CRP expression. Key findings of our research were: 1. IL-1β-activated NF-κB p50/p65 acted synergistically with IL-6-activated C/EBPβ in inducing CRP transactivation through the proximal CRP promoter. 2. A NF-κB site was localized in the proximal CRP promoter centered at position -69 overlapping the known OCT-1/HNF-1/HNF-3 sites. 3. The synergy between IL-6 and IL-1β in inducing CRP gene expression was partially mediated through the NF-κB site. 4. In the absence of C/EBPβ, a complex containing C/EBPζ and RBP-Jκ was formed at the C/EBP-p50-site. 5. Overexpressed C/EBPζ repressed both (IL-6+IL-1β)-induced and C/EBPβ-induced CRP expression. 6. OCT-1 repressed (IL-6+IL-1β)-induced CRP transactivation through the proximal CRP promoter. 7. Statins reduce cytokine-induced CRP gene expression at the transcriptional level. These findings led us to conclude that: 1. CRP transcription is determined by the relative levels of various transcription factors such as C/EBPβ, C/EBPζ, NF-κB and OCT-1 and their interaction with the proximal CRP promoter. 2. Inhibition of CRP transcription by statins is not due to an anti-inflammatory effect but due to the direct effect on CRP gene expression.
","abstract_html":"<p>C-reactive protein (CRP) is an acute phase protein produced by hepatocytes whose serum concentration increases in inflammatory conditions including cardiovascular complications. Statins that are used in the treatment of cardiovascular diseases to reduce cholesterol also lower serum CRP levels. In human hepatoma Hep3B cells, CRP is induced in response to cytokines IL-6 and IL-1β. The objective of the study was to determine the mechanism of regulation of CRP gene expression in Hep3B cells in response to cytokines and to determine the effect of statins on CRP expression. Key findings of our research were: 1. IL-1β-activated NF-κB p50/p65 acted synergistically with IL-6-activated C/EBPβ in inducing CRP transactivation through the proximal CRP promoter. 2. A NF-κB site was localized in the proximal CRP promoter centered at position -69 overlapping the known OCT-1/HNF-1/HNF-3 sites. 3. The synergy between IL-6 and IL-1β in inducing CRP gene expression was partially mediated through the NF-κB site. 4. In the absence of C/EBPβ, a complex containing C/EBPζ and RBP-Jκ was formed at the C/EBP-p50-site. 5. Overexpressed C/EBPζ repressed both (IL-6+IL-1β)-induced and C/EBPβ-induced CRP expression. 6. OCT-1 repressed (IL-6+IL-1β)-induced CRP transactivation through the proximal CRP promoter. 7. Statins reduce cytokine-induced CRP gene expression at the transcriptional level. These findings led us to conclude that: 1. CRP transcription is determined by the relative levels of various transcription factors such as C/EBPβ, C/EBPζ, NF-κB and OCT-1 and their interaction with the proximal CRP promoter. 2. Inhibition of CRP transcription by statins is not due to an anti-inflammatory effect but due to the direct effect on CRP gene expression.</p>","abstract_has_math":false,"creators":["Voleti, Bhavya"],"institution":null,"degree_name":"PhD (Doctor of Philosophy)","degree_level":"Dissertation - unrestricted","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007-12-15T08:00:00Z","date_published":"2007-12-15T08:00:00Z","updated_at":"2026-07-24T02:21:19Z","subjects":["C-reactive protein","Acute phase response","Transcription factors","Gene expression","Inflammation","Genetics and Genomics","Life Sciences","Molecular Genetics"],"languages":[],"rights":["Copyright by the authors."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.etsu.edu/etd/2058","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Voleti, Bhavya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2007-12-15T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation - unrestricted"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD (Doctor of Philosophy)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["C-reactive protein","Acute phase response","Transcription factors","Gene expression","Inflammation","Genetics and Genomics","Life Sciences","Molecular Genetics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Copyright by the authors."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.etsu.edu/context/etd/article/3419/viewcontent/VoletiB121107f.pdf","https://dc.etsu.edu/etd/2058"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["C-reactive protein (CRP) is an acute phase protein produced by hepatocytes whose serum concentration increases in inflammatory conditions including cardiovascular complications. Statins that are used in the treatment of cardiovascular diseases to reduce cholesterol also lower serum CRP levels. In human hepatoma Hep3B cells, CRP is induced in response to cytokines IL-6 and IL-1β. The objective of the study was to determine the mechanism of regulation of CRP gene expression in Hep3B cells in response to cytokines and to determine the effect of statins on CRP expression. Key findings of our research were: 1. IL-1β-activated NF-κB p50/p65 acted synergistically with IL-6-activated C/EBPβ in inducing CRP transactivation through the proximal CRP promoter. 2. A NF-κB site was localized in the proximal CRP promoter centered at position -69 overlapping the known OCT-1/HNF-1/HNF-3 sites. 3. The synergy between IL-6 and IL-1β in inducing CRP gene expression was partially mediated through the NF-κB site. 4. In the absence of C/EBPβ, a complex containing C/EBPζ and RBP-Jκ was formed at the C/EBP-p50-site. 5. Overexpressed C/EBPζ repressed both (IL-6+IL-1β)-induced and C/EBPβ-induced CRP expression. 6. OCT-1 repressed (IL-6+IL-1β)-induced CRP transactivation through the proximal CRP promoter. 7. Statins reduce cytokine-induced CRP gene expression at the transcriptional level. These findings led us to conclude that: 1. CRP transcription is determined by the relative levels of various transcription factors such as C/EBPβ, C/EBPζ, NF-κB and OCT-1 and their interaction with the proximal CRP promoter. 2. Inhibition of CRP transcription by statins is not due to an anti-inflammatory effect but due to the direct effect on CRP gene expression.
"]},{"key":"dc:title","label":"Title","values":["Mechanism of Transcriptional Regulation of C-Reactive Protein Gene Expression."]}]}],"canonical_facts":{"dc:creator":["Voleti, Bhavya"],"dc:date.issued":["2007-12-15T08:00:00Z"],"dc:description.abstract":["C-reactive protein (CRP) is an acute phase protein produced by hepatocytes whose serum concentration increases in inflammatory conditions including cardiovascular complications. Statins that are used in the treatment of cardiovascular diseases to reduce cholesterol also lower serum CRP levels. In human hepatoma Hep3B cells, CRP is induced in response to cytokines IL-6 and IL-1β. The objective of the study was to determine the mechanism of regulation of CRP gene expression in Hep3B cells in response to cytokines and to determine the effect of statins on CRP expression. Key findings of our research were: 1. IL-1β-activated NF-κB p50/p65 acted synergistically with IL-6-activated C/EBPβ in inducing CRP transactivation through the proximal CRP promoter. 2. A NF-κB site was localized in the proximal CRP promoter centered at position -69 overlapping the known OCT-1/HNF-1/HNF-3 sites. 3. The synergy between IL-6 and IL-1β in inducing CRP gene expression was partially mediated through the NF-κB site. 4. In the absence of C/EBPβ, a complex containing C/EBPζ and RBP-Jκ was formed at the C/EBP-p50-site. 5. Overexpressed C/EBPζ repressed both (IL-6+IL-1β)-induced and C/EBPβ-induced CRP expression. 6. OCT-1 repressed (IL-6+IL-1β)-induced CRP transactivation through the proximal CRP promoter. 7. Statins reduce cytokine-induced CRP gene expression at the transcriptional level. These findings led us to conclude that: 1. CRP transcription is determined by the relative levels of various transcription factors such as C/EBPβ, C/EBPζ, NF-κB and OCT-1 and their interaction with the proximal CRP promoter. 2. Inhibition of CRP transcription by statins is not due to an anti-inflammatory effect but due to the direct effect on CRP gene expression.
"],"dc:identifier":["https://dc.etsu.edu/context/etd/article/3419/viewcontent/VoletiB121107f.pdf","https://dc.etsu.edu/etd/2058"],"dc:rights":["Copyright by the authors."],"dc:subject":["C-reactive protein","Acute phase response","Transcription factors","Gene expression","Inflammation","Genetics and Genomics","Life Sciences","Molecular Genetics"],"dc:title":["Mechanism of Transcriptional Regulation of C-Reactive Protein Gene Expression."],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation - unrestricted"],"thesis:degree_name":["PhD (Doctor of Philosophy)"]},"updated_at":"2026-07-24T02:21:19Z"}