2026-09-23T12:22:16Zhttps://repository.ajou.ac.kr/oai/request

oai:repository.ajou.ac.kr:201003/13882024-10-11T02:17:30Zcom_201003_14369com_201003_14368col_201003_14370

주, 일로 이, 창석 대학원 의학과 200424202 이, 창석 2011-01-31T05:54:37Z 2011-01-31T05:54:37Z 2006 2006 http://repository.ajou.ac.kr/handle/201003/1388 http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001229 000000001229 "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." Approved for entry into archive by Hyun Chul Cho (hccho@ajou.ac.kr) on 2011-01-31T05:54:37Z (GMT) No. of bitstreams: 1 000000001229.pdf: 915632 bytes, checksum: fcf36e773f162dd914d1f601d0e56d12 (MD5) Made available in DSpace on 2011-01-31T05:54:37Z (GMT). No. of bitstreams: 1 000000001229.pdf: 915632 bytes, checksum: fcf36e773f162dd914d1f601d0e56d12 (MD5) Submitted by Hyun Chul Cho (hccho@ajou.ac.kr) on 2011-01-31T05:54:37Z No. of bitstreams: 1 000000001229.pdf: 915632 bytes, checksum: fcf36e773f162dd914d1f601d0e56d12 (MD5) "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 text/plain en Anti-Inflammatory Mechanism By Oxysterols In Cultured Rat Brain Astrocytes 성상교세포에서 옥시스테롤의 항염증반응에 대한 연구 Thesis Theses oxysterols LXR iNOS IFN-gamma STAT IRF-1 astrocytes 2006 9999-12-31 9999-12-31