Regulation of T helper cell responses by costunolide via down-regulation of dendritic cells' maturation|RISS 상세보기

다국어 초록 (Multilingual Abstract)

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-gproduction 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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목차 (Table of Contents)

LIST OF FIGURES 6
LIST OF ABBREVIATION 7
ABSTRACT 8
I. INTRODUCTION 10
II. MATERIALS AND METHODS 16

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

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Regulation of T helper cell responses by costunolide via down-regulation of dendritic cells' maturation

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