성상교세포에서 옥시스테롤의 항염증반응에 대한 연구
DC Field | Value | Language |
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dc.contributor.advisor | 주일로 | - |
dc.contributor.author | 이창석 | - |
dc.date.accessioned | 2019-10-21T06:47:39Z | - |
dc.date.available | 2019-10-21T06:47:39Z | - |
dc.date.issued | 2006-02 | - |
dc.identifier.other | 1229 | - |
dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/16781 | - |
dc.description | 학위논문(석사)--아주대학교 일반대학원 :의학과,2006. 2 | - |
dc.description.tableofcontents | 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 | - |
dc.language.iso | eng | - |
dc.publisher | The Graduate School, Ajou University | - |
dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
dc.title | 성상교세포에서 옥시스테롤의 항염증반응에 대한 연구 | - |
dc.title.alternative | Lee Chang Seok | - |
dc.type | Thesis | - |
dc.contributor.affiliation | 아주대학교 일반대학원 | - |
dc.contributor.alternativeName | Lee Chang Seok | - |
dc.contributor.department | 일반대학원 의학과 | - |
dc.date.awarded | 2006. 2 | - |
dc.description.degree | Master | - |
dc.identifier.localId | 565079 | - |
dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229 | - |
dc.description.alternativeAbstract | 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. | - |
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