Interferon-gamma suppresses melanogenesis in B16 melanoma cells and primary human melanocytes
배양 세포주를 이용한 인터페론 감마의 색소형성 억제효과 및 기전에 관한 연구
- 주제(키워드) Melanogenesis , alpha-MSH , IFN-gamma , Tyrosinase , MITF , STAT1 , CBP , CREB
- 발행기관 아주대학교
- 지도교수 주일로
- 발행년도 2013
- 학위수여년월 2013. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000013983
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Inflammatory cytokines are closely related to melanogenesis in melanocytes. Here, I studied whether IFN-γ affects melanogenesis, and if so, what is the underlying mechanism involved in it. Using B16 melanoma cell lines and primary human melanocytes, I demonstrated that alpha-MSH induced tyrosinase expression and activity and TRP-1, TRP-2 expression were suppressed by IFN-γ, which resulted from the inhibition of MITF expression, upstream molecule of tyrosinase. Moreover, the inhibitory effects on MITF expression by IFN-γ occured through the disturbance of CREB binding ability on MITF promoter by reducing the binding of CBP and CREB. These results suggest that IFN-γ decreases melanogenesis through inhibiting the binding of CBP and CREB and block the MITF and tyrosinase expression.
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TABLE OF CONTENTS
ABSTRACT i
TABLE OF CONTENTS ii
LIST OF FIGURES v
ABBREVIATION vii
Ⅰ. INTRODUCTION １
Ⅱ. MATERIALS AND METHODS ５
A. Cell culture ５
B. Reagent ５
C. Tyrosinase activity ６
D. Western immunoblot analysis ６
E. RNA extraction and real-time PCR ７
F. Melanin content ７
G. Electrophoresis mobility shift assays (EMSA) ７
H. Duolink assay ８
Ⅲ. RESULTS ９
A. IFN-γ suppresses tyrosinase expression in B16 melanoma cells ９
B. IFN-γ does not affect degradation of tyrosinase in B16 melanoma cells １１
C. IFN-γ inhibits tyrosinase activity and melanin production in B16 melanoma cells １１
D. IFN-γ suppresses the tyrosinase expression and activity in primary human melanocytes １４
E. IFN-γ suppresses MITF binding ability in B16 melanoma cells １４
F. IFN-γ inhibits MITF expression in B16 melanoma cells １８
G. IFN-γ does not regulate MITF mRNA stability in B16 melanoma cells １８
H. CREB binding on promoter of MITF is decreased by IFN-γ treatment ２１
I. JAK-STAT signaling may be involved in the IFN-γ induced inhibitor of melanogemesis ２１
Ⅳ. DISCUSSION ２８
Ⅴ. CONCLUSION ３５
REFERENCES ３６
국문요약 ４０
