repository
Graduate School of Ajou University
Department of Neuroscience and Technology Course
3. Theses(Master)
Regulation of IFN-gamma induced Inflammatory Response in Rat Brain Astrocytes
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Joe, Eun Hye | - |
| dc.contributor.author | 전새봄 | - |
| dc.date.accessioned | 2019-10-21T06:46:04Z | - |
| dc.date.available | 2019-10-21T06:46:04Z | - |
| dc.date.issued | 2005 | - |
| dc.identifier.other | 267 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/16389 | - |
| dc.description | 학위논문(석사)--아주대학교 대학원 :신경과학기술협동과정,2005 | - |
| dc.description.abstract | Janus kinase (JAK)과 signal transducers and activators of transcription (STAT)은 중요한 염증성 cytokine인 IFN-gamma의 염증반응을 매개하는 주요한 경로이다. 따라서, JAK/STAT 경로의 조절은 IFN-gamma에 의해 유도되는 염증반응을 조절하는데 중요하다. 본 연구에서 우리는 lipoxygenase (LO) 억제제로 잘 알려져 있는 nordihydroguaiaretic acid (NDGA) 가 뇌신경교세포에서 IFN-gamma에 의해 유도된 염증반응을 억제함을 밝혔다. NDGA가 존재할 때, IFN-gamma에 의해 증가된 interferon regulatory factor-1 (IRF-1) 과 interferon inducing protein-10 (IP-10) 의 발현이 감소하였다. 또한, NDGA는 JAK과 STAT의 tyrosine 인산화를 억제하였다. 그러나, IFN-gamma를 처리한 세포에서 5-LO의 주요한 생성물인 leukotriene B₄ (LTB₄) 와 leukotriene C₄ (LTC₄) 가 생성되지 않고, 다른 5-LO 억제제인 Rev5901과 AA861이 NDGA의 효과를 모방하지 않는 것으로 보아 NDGA의 효과는 5-LO를 억제하는 작용과는 독립적으로 나타나는 효과로 보인다. 게다가, 5-LO의 주요한 대사 산물인 5-hydroxyeicosatetraenoic acid (5-HETE) 와 LTB4가 NDGA에 의한 STAT활성화의 억제를 반전시키지 못했다. 따라서 이러한 결과는 NDGA가 IFN-gamma에 의해 유도되는 염증반응을 조절하는데, 5-LO 억제 기전과는 관계없이 나타나는 현상임을 제시한다. | - |
| dc.description.tableofcontents | TABLE OF CONTENTS ABSTRACT = i TABLE OF CONTENTS = ⅱ LIST OF FIGURES = ⅳ Ⅰ. INTRODUCTION = 1 Ⅱ. MATERIALS AND METHODS = 5 A. Reagents = 5 B. Preparation of cells = 5 C. Reverse Transcription and Polymerase Chain Reaction (RT-PCR) = 6 D. Western Blot Analysis = 7 E. LTB₄, and LTC₄ Assay = 7 F. Stereotaxic injection of IFN-γ = 8 Ⅲ. RESULTS = 9 A. Nordihydroguaiaretic acid (NDGA) suppressed IFN-γ-induced inflammatory responses in brain glial cells = 9 1. NDGA reduced IFN-γ-induced activation of STAT1 and STAT3 in brain glial cells = 9 2. NDGA reduced IFN-γ-induced JAK2 activation in brain glial cells = 10 3. NDGA reduced IFN-γ-induced IRF-1 and IP-10 expression in brain glial cells = 10 B. NDGA suppressed IFN-γ-induced inflammatory responses in vivo = 14 1. NDGA reduced IFN-γ-mediated inflammatory response in vivo = 14 C. NDGA suppressed IFN-γ-induced STAT phosphorylation independently of lipoxygenase inhibition = 14 1. IFN-γ produced neither LTB4 nor LTC₄ = 14 2. Effect of Rev5901, AA861, baicalein on IFN-γ-induced STAT phosphorylation 15 3. Products of 5-LO did not reverse the inhibitory effect of NDGA = 19 Ⅳ. DISCUSSION = 21 Ⅴ. CONCLUSION = 24 REFERENCES = 25 국문요약 = 34 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Regulation of IFN-gamma induced Inflammatory Response in Rat Brain Astrocytes | - |
| dc.title.alternative | Astrocytes에서 IFN-gamma에 의한 염증반응 조절연구 | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | 전새봄 | - |
| dc.contributor.department | 일반대학원 신경과학기술과정 | - |
| dc.date.awarded | 2005. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 564515 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000267 | - |
| dc.description.alternativeAbstract | Janus kinase (JAK) and signal transducers and activators of transcription (STAT) are major pathways that mediate inflammatory functions of interferon-γ (IFN-γ), a prominent pro-inflammatory cytokine. Therefore, it is required to regulate JAK/STAT signaling pathways to modulate IFN-γ-mediated inflammation. In this study, I revealed that nordihydroguaiaretic acid (NDGA), a well known lipoxygenase (LO) inhibitor, suppressed IFN-γ-induced inflammatory responses in brain glial cells. In the presence of NDGA, IFN-γ-induced IRF protein expression and MCP-1 and IP-10 mRNA expression were suppressed. NDGA also suppressed tyrosine-phosphorylation of JAK and STAT. However, the effect of NDGA seemed to be independent of inhibition of 5-LO since none of 5-LO products, leukotriene B4 (LTB₄) and leukotriene C4 (LTC₄), was detected in cells treated with IFN-γ. Other 5-LO inhibitors (Rev5901 and AA861) did not mimic the effect of NDGA. In addition, none of 5-LO metabolites, 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB₄), reversed NDGA-driven suppression of STAT activation or affect basal STAT phosphorylation. Taken together, these results suggest that NDGA regulate IFN-γ-mediated inflammation through the mechanisms unrelated to the inhibition of 5-LO. | - |
- Appears in Collections:
- Graduate School of Ajou University > Department of Neuroscience and Technology Course > 3. Theses(Master)
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
-
- License
- STATISTICS
- Total Visit :3,867,950
- Total Download :1,953
- Today View :4,728
