(+)-Nootkatone inhibits TNF-α/IFN-γ- induced production of chemokines in human keratinocytes
- 주제(키워드) (+)-nootkatone , TARC/CCL17 , MDC/CCL22 , HaCaT cells , atopic dermatitis
- 발행기관 아주대학교
- 지도교수 정이숙
- 발행년도 2014
- 학위수여년월 2014. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학
- 실제URI http://www.dcollection.net/handler/ajou/000000016511
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Atopic dermatitis (AD) is a inflammatory skin disease associated with allergy and it is commonly characterized with skin dry, severe pruritus, high serum IgE levels and eosinophilia. Keratinocytes produce many chemokines which are involved in the pathogenesis of skin disorders. In particular, thymus and activation-regulated chemokine (TARC/CCL17) & macrophage-derived chemokine (MDC/CCL22) are Th2-type chemokines, and it has been reported that serum TARC and MDC levels are associated with AD disease activity. (+)-Nootkatone is the major component of Cyperus rotundus. (+)-Nootkatone has antiallergic, anti-inflammatory, and antiplatelet activities. The purpose of this study was to investigate the effect of (+)-nootkatone on tumor necrosis factor α (TNF-α)/interferon γ (IFN-γ)-induced expression of Th2 chemokines in HaCaT cells. We found that (+)-nootkatone inhibited the TNF-α/IFN-γ-induced expression of CCL17 and CCL22 mRNA in HaCaT cells. It also significantly inhibited TNF-α/IFN-γ-induced activation of nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), and protein kinase C zeta (PKC ζ). Furthermore, we showed that PKC ζ and p38 MAPK contributed to the inhibition of TNF-α/IFN-γ-induced CCL17 and CCL22 expression by blocking IκBα degradation in HaCaT cells. Taken together, these results suggest that (+)-nootkatone may suppress TNF-α/IFN-γ-induced CCL17 and CCL22 expression in HaCaT cells by inhibiting of PKC ζ and p38 MAPK signaling pathways that lead to activation of NF-κB. We propose that (+)-nootkatone may be a useful therapeutic candidate for inflammatory skin diseases such as AD.
more목차
Abstract i
TABLE OF CONTENTS iii
LIST OF FIGURES v
ABBREVIATION vi
Ⅰ. INTRODUCTION 1
A. Atopic dermatitis (AD) 1
B. The role of TARC/CCL17 and MDC/CCL22 2
C. Antiallergic therapy in atopic dermatitis 2
D. (+)-Nootkatone 3
E. Aims of study 4
Ⅱ. MATERIALS AND METHODS 5
A. Materials 5
B. Cell cultures 5
C. Cell viability assay 6
D. Reverse transcriptase polymerase chain reaction 6
E. Western blotting 7
F. Immunocytochemistry 8
G. Statistical analysis 9
Ⅲ. RESULTS 10
A. (+)-Nootkatone inhibited TNF-α/IFN-γ-induced
expression of CCL17 and CCL22 in HaCaT cell 10
B. p38 MAPK involved to TNF-α/IFN-γ-induced CCL17 and
CCL22 expression in HaCaT cells 12
C. (+)-Nootkatone inhibited TNF-α/IFN-γ-induced
activation of p38 MAPK in HaCaT cells 14
D. PKC ζ involved to TNF-α/IFN-γ-induced CCL17 and
CCL22 expression in HaCaT cells 16
E. (+)-Nootkatone inhibited TNF-α/IFN-γ-induced
activation of PKC ζ in HaCaT cells 18
F. NF-κB involved to TNF-α/IFN-γ-induced CCL17 and
CCL22 expression in HaCaT cells 20
G. (+)-Nootkatone inhibited TNF-α/IFN-γ-induced
degradation of IκBα in HaCaT cells 22
H. (+)-Nootkatone inhibited TNF-α/IFN-γ-induced
translocation of NF-κB in HaCaT cells 24
Ⅳ. DISCUSSION 26
Ⅴ. CONCLUSION 29
REFERENCES 30
국문요약 37
