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Interferon-gamma suppresses melanogenesis in B16 melanoma cells and primary human melanocytes

Other Title
배양 세포주를 이용한 인터페론 감마의 색소형성 억제효과 및 기전에 관한 연구
Authors
손, 진영
Degree
Master (2013)
Abstract
멜라닌은 DNA 손상을유도하는 UV 자극으로부터피부를보호한다. 최근 염증사이토카인이멜라닌생성억제와연관되어있다고보고된바있지만세부적인연구내용은아직 밝혀지지않았다. 본연구자는멜라닌형성에염증사이토카인인인터페론감마가멜라닌 색소생성에형성에미치는영향과그기전에관하여알아보았다. B16 악성흑색종세포와 사람피부멜라닌형성세포를이용하여a-MSH 에의하여유도된멜라닌형성에주요한효소인tyrosinase, TRP-1, TRP-2 의발현이인터페론 감마에의하여억제되는현상을확인하였으며tyrosinase의활성과 mRNA 발현이억제되는것을확인하였다. 이는tyrosinase 단백질의분해를통하여일어나는일은아님을밝혔다. 본연구자는인터페론감마가tyrosinase 의상위전사인자인 MITF의단백질과 RNA의발현또한억제하는것을확인하였다. RNA의발현억제현상은 RNA의안정성억제와는무관하였다. MITF는전사인자인 CREB에의하여전사가조절됨이알려져있으며본연구자는인터페론감마가 CREB의활성을억제함 을밝혔다. 또한인터페론 감마에의하여활성화되는 STAT1이 tyrosinase의발현억제에관여한다는사실을확인하였다. 활성화된 STAT1은 CREB의보조전사인자인 CBP와결함함으로써CBP와CREB과의결합을막아CREB의활성을떨어뜨리는것이밝혀졌다. 본연 구자는결과를통하여인터페론감마가 CBP와결합함으로써MITF의전사인자인 CREB 의활성을막아멜라닌형성을억제한다는사실을밝혀냈으며본연구는사이토카인에의한 멜라닌조절메커니즘을밝히는연구에상당부분기여할수있을것으로기대된다.

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. 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.
Keywords
Melanogenesisa-MSHIFN-gTyrosinaseMITFSTAT1CBPCREB
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Theses > Graduate School of Biomedical Sciences > Master
AJOU Authors
손, 진영
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