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신경 교세포에서 Peroxisome Proliferator-Activated Receptors (PPARs)의 작용기전과 효과에 대한 연구
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 주일로 | - |
| dc.contributor.author | 이지훈 | - |
| dc.date.accessioned | 2019-10-21T07:11:57Z | - |
| dc.date.available | 2019-10-21T07:11:57Z | - |
| dc.date.issued | 2007-08 | - |
| dc.identifier.other | 2457 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/17161 | - |
| dc.description | 학위논문(박사)----아주대학교 일반대학원 :의학과,2007. 8 | - |
| dc.description.tableofcontents | ABSTRACT TABLE OF CONTENTS LIST OF FIGURES ABBREVIATION Ⅰ. INTRODUCTION A. Brain inflammation B. PPARs 1. General functions and molecular mechanism of PPARs 2. PPARs in inflammation C. Aims of study Ⅱ. MATERIAL AND METHOD A. Reagents B. Cell cultures C. RNA isolation and Reverse Transcription Polymerase Chain Reaction (RT-PCR) D. Western blot analysis E. Electrophoresis Mobility Shift Assay (EMSA) F. Enzyme-Linked ImmunoSorbent Assay (ELISA) G. Immunoprecipitation H. Construction of luciferase reporter plasmids I. Transfection and luciferase assay J. Chromatin ImmunoPrecipitation (ChIP) assay K. Short interference RNA (siRNA) transfection L. Phosphatase assay M. Immunostaining and Confocal Microscopy N. In vitro ischemia Ⅲ. RESULTS A. PPAR-？ and -？ activators differentially regulate inflammatory genes in rat glial cells B. PPAR-？ and -？ activators suppressed activity of various transcription factors of MCP-1 gene in LPS- and IFN-？-activated glial cells C. PPAR-？ and -？ activators differentially regulate AP-1 and SP-1 signaling in IFN-？-activated rat astrocytes, not LPS D. MCP-1 expression is sufficiently induced by only AP-1 and SP-1 fragment of rat MCP-1 gene E. PPAR-？ and -？ activators differentially regulate MCP-1 expression by through regulating MKP-1 in IFN-？-activated astrocytes F. PPAR-？ and -？ activators suppress expression of MCP-1 gene in primary macrophage and RAW 264.7 cells, not microglia Ⅳ. DISCUSSION Ⅴ. CONCLUSION REFERENCES 국문요약 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | 신경 교세포에서 Peroxisome Proliferator-Activated Receptors (PPARs)의 작용기전과 효과에 대한 연구 | - |
| dc.title.alternative | JeeHoon Lee | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | JeeHoon Lee | - |
| dc.contributor.department | 일반대학원 의학과 | - |
| dc.date.awarded | 2007. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 566940 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000002457 | - |
| dc.subject.keyword | PPAR-gamma | - |
| dc.subject.keyword | PPAR-alpha | - |
| dc.subject.keyword | MCP-1 | - |
| dc.subject.keyword | AP-1 | - |
| dc.subject.keyword | SP-1 | - |
| dc.subject.keyword | MKP-1 | - |
| dc.subject.keyword | LPS | - |
| dc.subject.keyword | IFN-gamma | - |
| dc.description.alternativeAbstract | The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which were originally known to be involved in the regulation of lipid and glucose homeostasis. Recently, there has been increasing reports on the involvement of PPARs during inflammatory process, but the exact mechanisms of action are largely unknown. In this study, we tested the role of PPARs, PPAR-？ and -？, on the development of LPS- and IFN-？-mediated inflammation in cultured rat brain glial cell. In LPS-stimulated rat glial cells, we observed activators of PPAR-？ inhibited pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-？), interleukin-6 (IL-6), interleukin-1 beta (IL-1？) and monocyte chemoattractant proteins (MCP-1) through suppressing activation of STAT1. Along with LPS, we further investigated whether activators of PPAR-？ and -？ also suppressed expression of pro-inflammatory mediators in IFN-？-activated rat astrocytes. Activators of PPAR-？ inhibited pro-inflammatory mediators we also tested, including TNF-？, IL-6, and MCP-1. In contrast, those of PPAR-？ could not suppress the expressions and release of MCP-1. Since several transcription factors, including NF-？B, C/EBP, STAT and AP-1/SP-1, were involved in its expression, we tested which plays a key role in among them. Sequential deletion of promoters revealed that AP-1/SP-1 act as key players, which were further confirmed by chromatin immunoprecipitation (ChIP). In an experiment to further reveal the mechanisms involved, we found that the differential effects on AP-1/SP-1 were mediated by Jun N-terminal kinase (JNK) and MAP kinase phosphatase-1 (MKP-1), upstream molecules of them. Taken together, these results show that signaling of MCP-1 expression differ from stimulus, such as LPS and IFN-？, and their production was differentially regulated by activators of PPAR-？ and ？？, which were ascribed to their effects on AP-1/SP-1, JNK and MKP-1, explaining more potent anti-inflammtory effects of PPAR-？ than -？ activators. | - |
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