뇌혈관세포에서 Chrysin에 의한 염증성 접합분자 발현 억제효과 및 기전
Inhibitory Effects of Chrysin on LPS-induced Expression of Adhesion Molecules in Brain Endothelial Cells
- 주제(키워드) Chrysin , Neuroinflammation , VCAM-1 , Lipopolysaccharide , Multiple sclerosis , Brain endothelial cells
- 발행기관 아주대학교
- 지도교수 정이숙
- 발행년도 2015
- 학위수여년월 2015. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학
- 실제URI http://www.dcollection.net/handler/ajou/000000018893
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Adhesion of leukocytes to endothelial cells plays an important role in the progression of neuroinflammation. Therefore, suppression of adhesion molecules expression in brain endothelial cells may contribute to inhibition of neuroinflammation. Chrysin (5,7-dihydroxyflavone) is a flavonoid component of propolis, blue passion flower and fruits. In the present study, we examined the effects of chrysin on lipopolysaccharide-induced expression of VCAM-1 in mouse cerebral vascular endothelial (bEnd.3) cells. In bEnd.3 cells, LPS increased mRNA expression of VCAM-1 in time-dependent manner. Crysin significantly decreased LPS-induced mRNA expression of VCAM-1. Chrysin also remarkably reduced protein expression of VCAM-1 in a concentration-dependent manner. Furthermore, chrysin dramatically blocked adhesion of U937 (monocytes) to bEnd.3 cells induced by LPS. Nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which are activated by LPS, were significantly inhibited by chrysin. These results indicate that chrysin inhibits the expression of VCAM-1 in brain endothelial cells through inhibition of NF-κB translocation and MAPK pathway, resulting in an attenuation of leukocytes adhesion to endothelial cells. The anti-neuroinflammatory effects of chrysin suggests a possible therapeutic application of this agent in neurodegenerative diseases such as septic encephalopathy, multiple sclerosis and allergic encephalomyelitis.
more목차
Abstract i
TABLE OF CONTENTS ii
LIST OF FIGURES iii
ABBREVIATION vi
Ⅰ. INTRODUCTION 1
A. Multiple sclerosis (MS) 1
B. The role of VCAM-1 on MS 2
C. Chrysin 2
D. Aims of study 3
Ⅱ. MATERIALS AND METHODS 4
A. Cell culture and reagents 4
B. Reverse-transcription polymerase chain reaction 5
C. Western blotting 5
D. Immunocytochemistry 6
E. Adhesion assay 7
F. Statistical analysis 7
Ⅲ. RESULTS 8
A. LPS-induced VCAM-1 mRNA expression in bEnd.3 cells 8
B. Chrysin inhibited LPS-induced VCAM-1 mRNA expression in bEnd.3 cells 10
C. LPS-induced VCAM-1 protein expression in bEnd.3 cells 11
D. Chrysin inhibited LPS-induced VCAM-1 protein expression in bEnd.3 cells 13
E. Chrysin inhibited U937 cells attachment to LPS-induced VCAM-1 protein expression in bEnd.3 cells 16
F. NF-κB involved to LPS-induced VCAM-1 expression in bEnd.3 cells 18
G. Chrysin inhibited LPS-induced NF-κB translocation in bEnd.3 cells 20
H. p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) involved to LPS-induced VCAM-1 expression in bEnd.3 cells 21
I. Chrysin inhibited LPS-induced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) in bEnd.3 cells 21
Ⅳ. DISCUSSION 26
Ⅴ. CONCLUSION 30
REFERENCES 31
국문요약 35
