THP-1 세포에서 유로텐신II 억제에 의한 ABCA1 발현 조절 기전
Urotensin II blockade recovers ABCA1 expression through ERK/IL-1ß inhibition in human THP-1 cells
- 주제(키워드) Atherosclerosis , Urotensin II , Urotensin II receptor , Urotensin II receptor antagonist , Interleukin-1 ß
- 발행기관 아주대학교
- 지도교수 정이숙
- 발행년도 2016
- 학위수여년월 2016. 8
- 학위명 석사
- 학과 및 전공 일반대학원 약학
- 실제URI http://www.dcollection.net/handler/ajou/000000023036
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Urotensin II (UII), the most potent vasoconstrictor peptide identified to date, is expressed at high level in vascular smooth muscle cells (VSMC) and endothelial cells whereas urotensin II receptor (UT) is abundant in monocytes and macrophages of atherosclerotic lesions. UII is highly expressed in the coronary arteries of the atherosclerotic patients compared to normal subjects. Recently, UII was shown to down-regulate ATP binding cassette transporter-A1 (ABCA1) expression, which is responsible for reverse cholesterol transportation in macrophages of atherosclerotic lesions. However, the mechanism was not elucidated clearly. Previous studies revealed that proinflammatory cytokine interleukin-1b (IL-1ß) repressed ABCA1 expression. To further find out the signaling pathway, we investigated whether IL-1ß is associated in UII-induced ABCA1 down-regulation. Our further results provided that UII receptor antagonist (KR-36676) decreased IL-1ß production and significantly recovered ABCA1 expression in mRNA and protein level. UII receptor antagonists was shown to protect atherosclerosis in animal and cell models in previous investigations. Our results implies that UII receptor antagonist (KR-36676) might be possible potent candidate for atherosclerosis by recovering ABCA1 expression via ERK/IL-1ß pathway.
more목차
I. INTRODUCTION 1
A. Atherosclerosis 1
B. Urotensin II 1
C. ABCA1 2
D. Urotensin II and ABCA1 3
E. Urotensin II receptor antagonist 3
F. Aims of the study 4
II. MATERIALS AND METHODS 5
A. Chemicals and Reagents 5
B. Cell culture 5
C. RNA isolation and Reverse Transcription- Polymerase Chain Reaction 6
D. Western immunoblotting analysis 6
E. Statistical analysis 7
III. RESULTS 8
A. UII-induced IL-1ß expression and effects of KR 36676, UII receptor inhibitor in UII-induced IL-1ß cytokine production 8
B. UII receptor antagonism recovers ABCA1 expression in THP-1 macrophages 10
C. Inhibition of ERK activation by UII antagonist KR-36676 on THP-1 cells 12
D. UII dependent ERK/IL-1ß signaling pathway in the down-regulation of ABCA1 14
E. Urotensin II down-regulates ABCA1 through LXR-α and LXR-ß independent pathway 16
IV. DISCUSSION 18
V. CONCLUSION 22
REFERENCES 23
