Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Role of PKR and EGR-1 in Induction of Interleukin-S by Type B Trichothecene Mycotoxin Deoxynivalenol in the Human Intestinal Epithelial Cells

B형 트리코테센 곰팡이 독소 데옥시니발레놀에 의한 인체 장관 상피세포 염증성 인터루킨 8유도에서의 PKR과 EGR-1의 상호 역할 규명

  • Park, Seong-Hwan (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine) ;
  • Yang, Hyun (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine) ;
  • Choi, Hye-Jin (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine) ;
  • Park, Yeong-Min (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine) ;
  • Ahn, Soon-Cheol (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine) ;
  • Kim, Kwan-Hoi (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine) ;
  • Lee, Soo-Hyung (Microbial Safety Division, Department of Crop Life Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Ahn, Jung-Hoon (Korea Science Academy) ;
  • Chung, Duk-Hwa (Division of Applied Life Science, Graduate School of Gyeongsang National University) ;
  • Moon, Yu-Seok (Department of Medical Sciences, Medical Research Institute, Pusan National University School of Medicine)
  • 박성환 (부산대학교 의학전문대학원 의과학과 및 의학연구소) ;
  • 양현 (부산대학교 의학전문대학원 의과학과 및 의학연구소) ;
  • 최혜진 (부산대학교 의학전문대학원 의과학과 및 의학연구소) ;
  • 박영민 (부산대학교 의학전문대학원 의과학과 및 의학연구소) ;
  • 안순철 (부산대학교 의학전문대학원 의과학과 및 의학연구소) ;
  • 김관회 (부산대학교 의학전문대학원 의과학과 및 의학연구소) ;
  • 이수형 (농촌진흥청 농산물안전성부) ;
  • 안정훈 (한국과학영재학교) ;
  • 정덕화 (경상대학교 식품공학과) ;
  • 문유석 (부산대학교 의학전문대학원 의과학과 및 의학연구소)
  • Published : 2009.07.30
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Abstract

Mucosal epithelia sense external stress signals and transmit them to the intracellular cascade responses. Ribotoxic stress-producing chemicals such as deoxynivalenol (DON) or other trichothecene mycotoxins have been linked with gastrointestinal inflammatory diseases by Fusarium-contamination. The purpose of this study was to test the hypothesis that DON evokes the epithelial sentinel signals of RNA-dependent protein kinase (PKR) and early growth response gene 1 (EGR-1), which together contribute to the pro-inflammatory cytokine interleukin 8 (IL-8) in human intestinal epithelial cells. PKR suppression by the dominant negative PKR expression attenuated DON-stimulated interleukin-8 production. Moreover, 1L-8 transcriptional activation by DON was also reduced by PKR inhibition in the human intestinal epithelial cells. Treatment with the PKR inhibitor also suppressed EGR-1 promoter activity, mRNA and protein induction, although mitogen-activated protein (MAP) kinases such as extracellular signal-regulated protein kinases (ERK) 1/2, p38, c-Jun N-terminal Kinase (INK) were little affected or even enhanced in presence of a PKR inhibitor. These patterns were also compared in the EGR-1-suppressed cells, which showed much more suppressed production of 1L-8. All things taken into consideration, DON-activated sentinel signals of EGR-1 via PKR mediated interleukin-8 production in human intestinal epithelial cells, which provide insight into the possible general mechanism associated with mucosal inflammation as an intestinal toxic insult by ribotoxic trichothecene mycotoxins.

점막 상피는 외부 인자를 감지하는 최전선의 인식부위로서 외부스트레스 자극을 하부의 반응 신호로 전달하는 주요 세포이다. 리보솜독성 반응을 유발하는 데옥시니발레놀 (DON) 및 그 관련 곰팡이 독소는 푸자륨 곰팡이 오염에 의한 식중독성 소화기 염증성 질환과의 연관성이 알려 져 있다. 본 연구의 목적은 DON이 상피세포 감지 신호 전달 분자로서 PKR과 EGR-1이 관련 되고 이들이 상피세포에서의 염증성 사이토가인 인터루킨 8의 생성에 관련 된다는 가정 하에서 연구를 수행 하였다. PKR 발현의 세포내 작용 억제는 DON에 의해 유도되는 인터루킨 8의 생성을 감소시켰다. 또한 DON에 의한 IL-8 전사 활성화는 PKR 억제에 의하여 장관 상피세포에서 감소하였다. PKR 저해제의 처리는 EGR-1 promoter 활성, mRNA, 단백질 유도 등을 감소를 유발하였으며 MAP kinase (ERK1/2, p38, JNK)는 변화가 적거나 오히려 PKR 저해제의 전처리에 의하여 항진 되었다. 결론적으로 DON에 의해 자극된 감지신호인 EGR-1은 자체적으로 또는 PKR 신호를 경유하여 인터루킨8의 생산을 항진하는데 주요한 기능을 하였다. 이를 통하여 향후 리보솜 독성 반응과 관련된 소화기 염증유발의 주요한 기전을 제공하고 있다.

Keywords

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