{"id":{"repo_id":"ajou","oai_identifier":"oai:repository.ajou.ac.kr:201003/1388"},"canonical_url":"https://search.dev.ndltd.org/etd/ajou/oai:repository.ajou.ac.kr:201003/1388","repository":{"repo_id":"ajou","name":"Ajou University","base_url":"http://repository.ajou.ac.kr/oai/request"},"display":{"title":"Anti-Inflammatory Mechanism By Oxysterols In Cultured Rat Brain Astrocytes","abstract":"\"Cholesterols are enriched in the brain and can be oxidized to oxysterols by spontaneous or enzyme-mediated processes. Oxysterols are transport forms of cholesterols across cell membranes and the blood-brain barrier. Here, to elucidate the roles of oxysterols in brain inflammation, I treated lipopolysaccharides(LPS)- or interferon gamma(IFN-stimulated rat brain astrocytes with two oxysterols, 7-ketocholesterol and 22(R)-hydroxycholesterol. In LPS-stimulated astrocytes, both oxysterols suppressed inducible nitric oxide synthase expression and nitric oxide release as well as upstream signaling molecules including interferon-, phosphorylated signal transducer and activator of transcription 1/3, and interferon regulatory factor-1. And oxysterols also inhibited interleukin-6 and tumor necrosis factor  transcripts, and monocyte chemoattractant protein-1 release. Oxysterols are known as nuclear receptor liver X receptor agonists, and these inhibitory effects were observed with synthetic agonists of liver X receptor and retinoid X receptor in a similar manner. In addition, ATP-binding cassette transporter a1 transcription, LXR-induced target gene, was increased by addition of either oxysterol or LXR agonist. Thus, I conclude that these effects are mediated by LXR/RXR heterodimers. Next, these inhibitory effects of oxysterols also appeared and were potentiated by RXR agonist in IFN-stimulated astrocytes. Furthermore, iNOS expression was inhibited by oxysterols and synthetic LXR ligands in LPS-stimulated primary microglia as well as in LPS- or IFN-stimulated primary astrocytes. I conclude that oxysterols suppress inflammatory gene expression through LXR/RXR activation in activated rat brain glial cells and these results provide new insights into the roles of oxysterols in brain inflammation.\"","abstract_html":""Cholesterols are enriched in the brain and can be oxidized to oxysterols by spontaneous or enzyme-mediated processes. Oxysterols are transport forms of cholesterols across cell membranes and the blood-brain barrier. Here, to elucidate the roles of oxysterols in brain inflammation, I treated lipopolysaccharides(LPS)- or interferon gamma(IFN-stimulated rat brain astrocytes with two oxysterols, 7-ketocholesterol and 22(R)-hydroxycholesterol. In LPS-stimulated astrocytes, both oxysterols suppressed inducible nitric oxide synthase expression and nitric oxide release as well as upstream signaling molecules including interferon-, phosphorylated signal transducer and activator of transcription 1/3, and interferon regulatory factor-1. And oxysterols also inhibited interleukin-6 and tumor necrosis factor  transcripts, and monocyte chemoattractant protein-1 release. Oxysterols are known as nuclear receptor liver X receptor agonists, and these inhibitory effects were observed with synthetic agonists of liver X receptor and retinoid X receptor in a similar manner. In addition, ATP-binding cassette transporter a1 transcription, LXR-induced target gene, was increased by addition of either oxysterol or LXR agonist. Thus, I conclude that these effects are mediated by LXR/RXR heterodimers. Next, these inhibitory effects of oxysterols also appeared and were potentiated by RXR agonist in IFN-stimulated astrocytes. Furthermore, iNOS expression was inhibited by oxysterols and synthetic LXR ligands in LPS-stimulated primary microglia as well as in LPS- or IFN-stimulated primary astrocytes. I conclude that oxysterols suppress inflammatory gene expression through LXR/RXR activation in activated rat brain glial cells and these results provide new insights into the roles of oxysterols in brain inflammation."","abstract_has_math":false,"creators":["이, 창석"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["주, 일로","대학원 의학과","200424202"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-31T05:54:37Z","date_published":"2011-01-31T05:54:37Z","updated_at":"2026-07-24T00:51:19Z","subjects":["oxysterols","LXR","iNOS","IFN-gamma","STAT","IRF-1","astrocytes"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229","000000001229"],"render_values":[{"text":"http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229","href":"http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229","code":true},{"text":"000000001229","href":null,"code":true}]}]},"links":{"outbound_url":"http://repository.ajou.ac.kr/handle/201003/1388","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["주, 일로","대학원 의학과","200424202","이, 창석"]},{"key":"dc:creator","label":"Author","values":["이, 창석"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-01-31T05:54:37Z","2006"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Theses"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["oxysterols","LXR","iNOS","IFN-gamma","STAT","IRF-1","astrocytes"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://repository.ajou.ac.kr/handle/201003/1388","http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229","000000001229"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["\"Cholesterols are enriched in the brain and can be oxidized to oxysterols by spontaneous or enzyme-mediated processes. Oxysterols are transport forms of cholesterols across cell membranes and the blood-brain barrier. Here, to elucidate the roles of oxysterols in brain inflammation, I treated lipopolysaccharides(LPS)- or interferon gamma(IFN-stimulated rat brain astrocytes with two oxysterols, 7-ketocholesterol and 22(R)-hydroxycholesterol. In LPS-stimulated astrocytes, both oxysterols suppressed inducible nitric oxide synthase expression and nitric oxide release as well as upstream signaling molecules including interferon-, phosphorylated signal transducer and activator of transcription 1/3, and interferon regulatory factor-1. And oxysterols also inhibited interleukin-6 and tumor necrosis factor  transcripts, and monocyte chemoattractant protein-1 release. Oxysterols are known as nuclear receptor liver X receptor agonists, and these inhibitory effects were observed with synthetic agonists of liver X receptor and retinoid X receptor in a similar manner. In addition, ATP-binding cassette transporter a1 transcription, LXR-induced target gene, was increased by addition of either oxysterol or LXR agonist. Thus, I conclude that these effects are mediated by LXR/RXR heterodimers. Next, these inhibitory effects of oxysterols also appeared and were potentiated by RXR agonist in IFN-stimulated astrocytes. Furthermore, iNOS expression was inhibited by oxysterols and synthetic LXR ligands in LPS-stimulated primary microglia as well as in LPS- or IFN-stimulated primary astrocytes. I conclude that oxysterols suppress inflammatory gene expression through LXR/RXR activation in activated rat brain glial cells and these results provide new insights into the roles of oxysterols in brain inflammation.\"","\"ABSTRACT ⅰ TABLE OF CONTENTS ⅲ LIST OF FIGURES ⅴ LIST OF TABLES ⅵ ABBREVIATION ⅶ I. INTRODUCTION 1 A. Cholesterol in brain 1 B. Oxysterol metabolism 3 C. LXRs in cholesterol metabolism and inflammation 5 D. Aims of study 7 II. MATERIALS AND METHODS 8 A. Reagents 8 B. Cell culture 8 C. Western Blot Analysis 9 D. Determination of NO release 9 E. Reverse transcription-polymerase chain reaction (RT-PCR) 10 F. Enzyme-linked immunosorbent assay (ELISA) 10 G. Data analysis 11 III. RESULTS 12 A. Oxysterols suppress iNOS, COX2 expression and NO production in LPS-stimulated rat brain astrocytes. 12 B. Suppression of iNOS expression by oxysterols occurs in a LXR/RXR heterodimer-dependent manner. 15 C. Oxysterols and synthetic LXR agonists suppress the expression of IFN- transcripts, phosphorylated STATs, and IRF-1 expression in LPS- stimulated primary astrocytes. 18 D. Oxysterols and synthetic LXR agonists suppress not only iNOS expression but the expression of IL-6 and TNFtranscripts, and MCP-1 release in LPS-stimulated primary astrocytes. 20 E. Oxysterols and synthetic LXR agonists suppress also iNOS expression in IFN-stimulated primary astrocytes and LPS-stimulated primary microglia 23 IV. DISCUSSION 27 V. CONCLUSION 29 REFERENCES 30 국문요약 39\"","Master"]},{"key":"dc:format","label":"Dc Format","values":["text/plain"]},{"key":"dc:title","label":"Title","values":["Anti-Inflammatory Mechanism By Oxysterols In Cultured Rat Brain Astrocytes","성상교세포에서 옥시스테롤의 항염증반응에 대한 연구"]}]}],"canonical_facts":{"dc:contributor":["주, 일로","대학원 의학과","200424202","이, 창석"],"dc:creator":["이, 창석"],"dc:date":["2011-01-31T05:54:37Z","2006"],"dc:description":["\"Cholesterols are enriched in the brain and can be oxidized to oxysterols by spontaneous or enzyme-mediated processes. Oxysterols are transport forms of cholesterols across cell membranes and the blood-brain barrier. Here, to elucidate the roles of oxysterols in brain inflammation, I treated lipopolysaccharides(LPS)- or interferon gamma(IFN-stimulated rat brain astrocytes with two oxysterols, 7-ketocholesterol and 22(R)-hydroxycholesterol. In LPS-stimulated astrocytes, both oxysterols suppressed inducible nitric oxide synthase expression and nitric oxide release as well as upstream signaling molecules including interferon-, phosphorylated signal transducer and activator of transcription 1/3, and interferon regulatory factor-1. And oxysterols also inhibited interleukin-6 and tumor necrosis factor  transcripts, and monocyte chemoattractant protein-1 release. Oxysterols are known as nuclear receptor liver X receptor agonists, and these inhibitory effects were observed with synthetic agonists of liver X receptor and retinoid X receptor in a similar manner. In addition, ATP-binding cassette transporter a1 transcription, LXR-induced target gene, was increased by addition of either oxysterol or LXR agonist. Thus, I conclude that these effects are mediated by LXR/RXR heterodimers. Next, these inhibitory effects of oxysterols also appeared and were potentiated by RXR agonist in IFN-stimulated astrocytes. Furthermore, iNOS expression was inhibited by oxysterols and synthetic LXR ligands in LPS-stimulated primary microglia as well as in LPS- or IFN-stimulated primary astrocytes. I conclude that oxysterols suppress inflammatory gene expression through LXR/RXR activation in activated rat brain glial cells and these results provide new insights into the roles of oxysterols in brain inflammation.\"","\"ABSTRACT ⅰ TABLE OF CONTENTS ⅲ LIST OF FIGURES ⅴ LIST OF TABLES ⅵ ABBREVIATION ⅶ I. INTRODUCTION 1 A. Cholesterol in brain 1 B. Oxysterol metabolism 3 C. LXRs in cholesterol metabolism and inflammation 5 D. Aims of study 7 II. MATERIALS AND METHODS 8 A. Reagents 8 B. Cell culture 8 C. Western Blot Analysis 9 D. Determination of NO release 9 E. Reverse transcription-polymerase chain reaction (RT-PCR) 10 F. Enzyme-linked immunosorbent assay (ELISA) 10 G. Data analysis 11 III. RESULTS 12 A. Oxysterols suppress iNOS, COX2 expression and NO production in LPS-stimulated rat brain astrocytes. 12 B. Suppression of iNOS expression by oxysterols occurs in a LXR/RXR heterodimer-dependent manner. 15 C. Oxysterols and synthetic LXR agonists suppress the expression of IFN- transcripts, phosphorylated STATs, and IRF-1 expression in LPS- stimulated primary astrocytes. 18 D. Oxysterols and synthetic LXR agonists suppress not only iNOS expression but the expression of IL-6 and TNFtranscripts, and MCP-1 release in LPS-stimulated primary astrocytes. 20 E. Oxysterols and synthetic LXR agonists suppress also iNOS expression in IFN-stimulated primary astrocytes and LPS-stimulated primary microglia 23 IV. DISCUSSION 27 V. CONCLUSION 29 REFERENCES 30 국문요약 39\"","Master"],"dc:format":["text/plain"],"dc:identifier":["http://repository.ajou.ac.kr/handle/201003/1388","http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229","000000001229"],"dc:language":["en"],"dc:subject":["oxysterols","LXR","iNOS","IFN-gamma","STAT","IRF-1","astrocytes"],"dc:title":["Anti-Inflammatory Mechanism By Oxysterols In Cultured Rat Brain Astrocytes","성상교세포에서 옥시스테롤의 항염증반응에 대한 연구"],"dc:type":["Thesis","Theses"]},"updated_at":"2026-07-24T00:51:19Z"}