The role of S100A8 and S100A9 in interaction between bronchial epithelial cells and neutrophils = 기관지 상피세포와 호중구간의 상호작용에서 S100A8과 S100A9의 역할

다국어 초록 (Multilingual Abstract)

Allergic asthma is characterized by bronchoconstriction, allergen-specific IgE and bronchial inflammation. S100A8 and S100A9 are important proteins in the pathogenesis of allergic asthma. In this study, I examined that the pathogenic mechanism of asthma is associated with interaction of cytokine release in bronchial epithelial cells with constitutive apoptosis of neutrophils. S100A8 and S100A9 increased the secretion of MCP-1, IL-6 and IL-8 in a time and dose dependent manners. TLR4 was constitutively expressed in BEAS-2B cells. This secretion was suppressed by TLR4i, an inhibitor of TLR4, LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of ERK, SB202190, an inhibitor of p38 MAPK, an inhibitor of JNK, SP600125 and BAY-11-7085, NF-κB inhibitor. S100A8 and S100A9 induced activations of Akt, ERK, p38 MAPK and JNK activations in a time-dependent manner. Supernatants collected from bronchial epithelial cells after S100A8 and S100A9 treatment suppressed the apoptosis of normal and asthmatic neutrophils. The supernatants inhibited the cleaved caspase 3 and caspase 9. The co-culture of human neutrophils with BEAS-2B cells inhibited more neutrophil apoptosis after S100A8 and S100A9 treatment than co-culture of human neutrophils with BEAS-2B cells without S100A8 and S100A9. These findings improve understanding of the role of S100A8 and S100A9 in interaction between bronchial epithelial cells and neutrophils in allergic asthma and will enable elucidation of asthma pathogenesis.

목차 (Table of Contents)

• ABSTRACT = i
• TABLE OF CONTENTS = iii
• LIST OF FIGURES = ⅳ
• Ⅰ. INTRODUCTION = 1
• Ⅱ. MATERIALS AND METHODS = 6
• Ⅲ. RESULTS = 12
• Ⅳ. DISCUSSION = 39
• REFERENCES = 44
• 국문요지 = 51