초록

1형 당뇨병에서 췌장 소도 세포사멸의 effector가 IFNγ/TNFa synergism이라는 것의 증명하고 그 synergism의 차단 또는 sFasL를 이용한 1형 당뇨병을 80% 이상 예방/치료 하는 기술을 완성하며 IFNγ/TNFa synergism의 signal transduction, transcription control 등molecular mechanism을 규명한다

Abstract ▼

Apoptosis of pancreatic islet cells is the most critical step in the development of type 1 diabetes and probably also type2diabetes. However, the mechanism of the apoptosis of pancreatic islet cells and the final effectors in the process are largelyun known. The aim of the study was to elucidate the

Apoptosis of pancreatic islet cells is the most critical step in the development of type 1 diabetes and probably also type2diabetes. However, the mechanism of the apoptosis of pancreatic islet cells and the final effectors in the process are largelyun known. The aim of the study was to elucidate the real effectors in the apoptosis of pancreatic islet cells in type 1 diabetesand the molecular mechanism and signal transduction in the process of their death. We tried to prove the IFNg/TNFasynergism theory we have proposed. We also tried prevention of type 1 diabetes by blocking the synergism. We also tried to elucidate signal transduction of the cytokine synergism and apoptotic cascade in the process of apoptosis of pancreatic isletcells. We proved that IFN/TNF synergism is the final effector molecule in apoptosis of pancrestic islet cells both in vitro and invivo. We succeeded in inhibiting the development of diabetes by administration of anti-TNFa antibody or anti-IFNg/anti-IFNaantibody combination. We also inhibited type 1 diabetes by ex vivo treatment of diabetogenic lymphocytes with soluble Fas ligand. physiological function of soluble Fas ligand as a mediator of deletion of potentially dangerous memory Tlymphocytes was also found. The role of STAT1 activation, IRF-1 induction, activation of caspase-3, -8, -9 and induction ofcaspase-1, -11 were also clarified. These results will be used for the 2nd step of the research aiming at the real application of these results and synthesis of the pathogenesis of type 1 diabetes and type 2 diabetes in terms of pancreatic islet cell death

목차 Contents

• 표지...1
• 제출문...2
• 보고서 초록...3
• 요약문...4
• SUMMARY...6
• CONTENTS...7
• 목차...8
• 제 1 장. 서론...9
• 제 2 장. 국내외 기술개발 현황...12
• 제 3 장. 연구개발수행 내용 및 결과...14
• 제 4 장. 연구개발목표 달성도 및 대외기여도...17
• 제 5 장. 연구개발결과의 활용계획...19
• 제 6 장. 참고문헌...20
• 제 7 장. 발표 논문 list 및 논문 표지...22