Anatomy & Biological Anthropology (해부∙생물인류학)

Korean Association of Physical Anthropologists (대한체질인류학회)
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Inhibitory Effects of CD99-derived Peptide CD99CRIII3 on the Extravasation of Monocytes and Inflammatory Reactions in Contact Dermatitis Mouse Model

접촉성 피부염 마우스 모델에서 단핵구의 유출 및 염증 반응에 대한 CD99-유래 펩타이드 CD99CRIII3의 억제 효과

  • Ju, Hyun-Mi (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Park, Kyeong-Han (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University)
  • 주현미 (강원대학교 의학전문대학원 해부세포생물학교실) ;
  • 박경한 (강원대학교 의학전문대학원 해부세포생물학교실)
  • Received : 2018.10.04
  • Accepted : 2018.12.04
  • Published : 2018.12.31
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Abstract

Leucocyte extravasation has been known to play an important role in inflammatory reactions including contact dermatitis. Previous studies suggested that CD99 regulates ${\beta}1$ integrin activity and may be a novel therapeutic target molecule for inflammatory diseases. In this study, the effects of CD99-derived peptide, CD99CRIII3, on inflammatory reactions in contact dermatitis mouse model were investigated. CD99CRIII3 decreased ${\beta}1$-integrin activity in human monocytic U937 cells. CD99CRIII3 inhibited the adhesion of U937 monocytes to human umbilical vein endothelial cells and their extravasation through human umbilical vein endothelial cells. CD99CRIII3 reduced inflammation in the phorbol myristate acetate-induced contact dermatitis mice in a dose-dependent manner. These results indicate that CD99CRIII3 suppresses the extravasation of monocytes and inflammatory reactions in the animal model of the contact dermatitis, suggesting that CD99CRIII3 could be a new drug candidate against inflammatory skin diseases.

접촉피부염은 피부가 이물질과 접촉함으로써 일어나는 염증반응으로 백혈구 혈관외유출이 매우 중요한 역할을 한다는 것은 잘 알려진 사실이다. 선행연구 결과 CD99가 ${\beta}1$ 인테그린 의존적 메커니즘을 통하여 단핵구의 혈관외유출을 조절하며, 따라서 염증 질환에 대한 치료제 개발의 신규 표적 분자일 가능성이 제시되었다. 본 연구에서는 CD99 유래 펩타이드인 CD99CRIII3가 단핵구의 혈관외유출과 접촉피부염 생쥐 모델에서 염증 반응을 억제하는지를 조사하였다. 인간 단핵구 세포주인 U937를 CD99CRIII로 처리할 경우 농도의존적으로 ${\beta}1$ integrin의 활성도가 감소되었으며, 이 세포주의 사람제대정맥내피세포에의 부착과 혈관외유출도 억제되었다. 나아가 CD99CRIII3는 포르볼 미리스테이트 아세테이트 처리에 의해 유발된 생쥐 접촉피부염 모델에서 Evans Blue의 혈관투과와 귀조직 무게를 농도 의존적으로 억제하였다. 이러한 결과들은 CD99CRIII3가 단핵구의 혈관외유출과 접촉피부염 동물 모델에서 일어나는 염증반응을 억제함을 보여준다. 이와 같이, 본 연구는 CD99 유래 펩타이드가 피부 염증질환에 대한 치료제로 개발될 가능성이 있음을 제시한다.

Keywords

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