Regulation of T helper cell responses by costunolide via down-regulation of dendritic cells’ maturation
- 주제(키워드) Costunolide , Dendritic cells , T helper cell responses
- 발행기관 고려대학교 대학원
- 지도교수 김태성
- 발행년도 2014
- 학위수여년월 2014. 8
- 학위구분 석사
- 학과 일반대학원 생명과학과
- 원문페이지 68 p
- 실제URI http://www.dcollection.net/handler/korea/000000051571
- 본문언어 영어
- 제출원본 000045808808
초록/요약
Costunolide, a germacranolide sesquiterpene lactone which is one of the active ingredients in several medicinal plants, is well known with their potent anti-cancer, anti-microbial, anti-fungal and anti-inflammatory properties. Costunolide has the ability to inhibit the production of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor-a (TNF)-a, interleukin (IL)-6 and IL-1b in addition to their suppression on the activation of nuclear factor (NF)-kB and mitogen-activated protein kinase (MAPK) on macrophages. However, the effects of costunolide on dendritic cells (DCs) yet remain to be elucidated. In this study, I determined the effects of costunolide on the maturation and activation of lipopolysaccharide (LPS)-stimulated DCs by determining the expression of cell surface molecules, their cytokine expression and production, as well as T helper (Th) cell responses. Costunolide significantly down-regulated the expression level of cell surface molecules such as CD40, co-stimulatory molecules (CD80 and CD86), and MHC class II. Moreover, costunolide also inhibited the expression and the production of several cytokines on DCs. At the same time, costunolide-treated DCs also inhibited CD4+ T cells proliferation in the presence of antigen by decreasing IL-2-expressing cells. Furthermore, costunolide-treated DCs inhibited LPS-induced IFN-gproduction while increased the production of IL-4 and IL-17 in CD4+ T cells. The production of IFN-g was restored after IL-12 treatment. These findings demonstrate that costunolide could effectively inhibits LPS-induced maturation of DCs, and in the meantime, regulates Th responses by attenuates Th1 via the reduction of IL-12 production and enhances Th2 and Th17 on CD4+ T cells. Thus, costunolide may be able to exhibit its therapeutic use, especially in Th1-mediated immune diseases.
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LIST OF FIGURES 6
LIST OF ABBREVIATION 7
ABSTRACT 8
I. INTRODUCTION 10
II. MATERIALS AND METHODS 16
III. RESULTS 23
IV. DISCUSSION 48
V. FINAL CONCLUSION 53
VI. REFERENCES 54
VII. ABSTRACT (KOREAN) 65
VIII. ACKNOWLWDGEMENT 67
