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췌장염 병인론에서 선세포 cytokine 발현에 대한 활성산소와 NF-κB의 역할

Other Titles
 Role of reactive oxygen species and transcription factor NF-κB on cytokine production in pancreatic acinar cells : relation to 
Authors
 유지훈 
Issue Date
2002
Description
의과학사업단/석사
Abstract
[한글] 활성산소는 NF-κB를 활성화시키며, cerulein으로 유도된 급성 췌장염의 초기 단계에서 NF-κB 활성화가 된다고 알려져 있다. 나아가 NF-κB가 활성화되면 췌장염의 병인에 관여하는 염증성 cytokine 유전자 발현이 조절된다고 알려져 있다. 본 연구에서는 쥐에서 분리한 췌장 선세포를 이용하여 cerulein에 의해 활성산소 및 지질과산화물 생성이 증가하고, NF-κB 활성화 및 cytokine(IL-1β, IL-6) 발현이 유도되는지를 살펴보고, 또한 그 상관관계를 규명보고자 하였다. 연구결과 췌장 선세포에서 cerulein은 활성산소 및 지질과산화물 생성을 증가시켰으며, NF-κB가 활성화되었다. 또한 cerulein처치에 의하여 IL-1β 및 IL-6 mRNA와 단백의 발현이 증가하였다. IL-1β 및 IL-6의 발현 증가는 항산화제인 GSH, SOD, catalase 그리고 NF-κB 활성화의 억제제인 PDTC의 전처치에 의하여 농도 의존적으로 억제되었다. 결론적으로 췌장 선세포에서 cerulein에 의하여 증가하는 활성산소 및 NF-κB 활성에 의하여 친염증성 cytokine의 발현 증가가 조절됨을 알 수 있었다.
[영문] Reactive oxygen species (ROS) has been considered as an important regulator in the pathogenesis and development of pancreatitis and as an activator of transcription factor, nuclear factor-κB (NF-κB) regulating inflammatory cytokine gene expression. NF-κB activation was demonstrated in cerulein pancreatitis which rapidly induces an acute, edematous form of pancreatitis. Present study aims to investigate whether cerulein induces ROS generation, production of lipid peroxide (LPO), NF-κB activation and the expression of cytokines (IL-1β, IL-6) in pancreatic acinar cells, and whether these alterations are inhibited by antioxidants and an inhibitor of NF-κB activation. As a result, cerulein generated ROS and increased LPO production in acinar cells. It resulted in NF-κB activation and induction of cytokine gene expression in acinar cells. Cerulein-induced NF-κB activation was in parallel with IκB-α degradation. Both antioxidants(GSH, SOD, catalase) and NF-κB inhibitor(PDTC) inhibited cerulein-induced, oxidant-mediated alterations in acinar cells. In conclusion, ROS, generated by cerulein activates NF-κB, resulting in upregulation of inflammatory cytokines gene expression in acinar cells. Inhibition of NF-κB by scavenging ROS might alleviate the inflammatory response in pancreatic acinar cells by suppressing cytokine gene expression.
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 2. Thesis
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/127991
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