단순포진 바이러스로 유도한 베체트병 마우스모델에서 Poly I:C 에 의해 유도된 IL-15Rα의 항 염증 효과에 관한 연구
Anti-inflammatory Role of IL-15Rα Up-regulated by Poly I:C in Herpes Simplex Virus-induced Behcet's Disease-like Mouse Model
- 주제(키워드) Behcet's disease , IL-15Rα , Poly I:C , memory CD8+ T cells , Herpes Simplex virus , mouse model
- 발행기관 아주대학교
- 지도교수 손성향
- 발행년도 2012
- 학위수여년월 2012. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000012284
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Behcet’s disease (BD) is a chronic, multi-systemic disorder that has arthritic, intestinal, mucocutaneous, ocular, vascular, and central nervous system affects. Interleukin-15 receptor alpha (IL-15Rα) forms stable complex with IL-15 on the cell surface of activated monocytes and mediates the proliferation of memory CD8+ T cells. Recent studies informed that Polyinosinic:polycytidylic acid (Poly I:C) is an immunostimulant which boosts the generation of memory T cells though induction of IL-15 and IL-15Rα. We found that the frequencies of IL-15Rα were significantly lower in HSV-induced BD mouse model than control mice. Therefore, this study was conducted to determine whether Poly I:C supplementation could induce memory cells through up-regulation of IL-15Rα, and reduce inflammation in HSV-induced BD symptoms. To evaluate whether the expression of IL-15Rα could be increased by poly I:C in vivo, Poly I:C was administered into normal and BD mice. Then, Poly I:C administered BD mice were subsequently observed the change of symptoms until 17 days after the last injection. The frequencies of IL-15Rα and memory CD8+ T cells were significantly up-regulated in Poly I:C injected mice. Poly I:C improved the symptoms and decreased severity score through down-regulation of pro-inflammatory cytokines and elevated regulatory and memory T cells. In conclusion, these results suggest that IL-15Rα is an important factor for the regulation of symptoms in HSV-induced BD mice.
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TABLE OF CONTENTS
ABSTRACT ⅰ
TABLE OF CONTENTS Ⅲ
LIST OF FIGURE ⅴ
LIST OF TABLES ⅶ
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 3
A. Animal experiments 3
B. BD symptoms in a mouse model 3
C. In vivo administration of Poly I:C 4
D. Flow cytometric analysis of cell surface staining 4
E. ELISA 5
F. Reverse transcription PCR (RT-PCR) 5
G. Statistical analysis 6
Ⅲ. RESULTS 7
A. The frequencies of IL-15Rα expressing cells in BD mice compared with BDN mice 9
B. Poly I:C up-regulates expression of IL-15Rα in PBMC of normal mice 12
C. Poly I:C ameliorates HSV-induced BD symptoms 16
D. Poly I:C up-regulates the frequencies of IL-15Rα but not IL-7Rα (CD127) in BD mice 18
E. Poly I:C induces CD8+CD44+ memory T cells in BD mice 20
F. Poly I:C up-regulate CD122(IL-15/2Rβ) and CD8+CD122+ T cells in BD mice 24
G. Poly I:C down-regulates IL-23 receptor and IL-17A in BD mice 28
Ⅳ. DISCUSSION 30
Ⅴ. CONCLUSION 34
REFERENCES 36
국문요약 45
