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Phosphatidic acid에 의한 intercellular adhesion molecule-1 발현 조절에 관여한 MAPK와 PKC-${\delta}$의 역할
THE ROLE OF MAPK AND PKC-${\delta}$ IN PHOSPHATIDIC ACID-MEDIATED INTERCELLULAR ADHESION MOLECULE-1 EXPRESSION

조우성   (영남대학교 의과대학 치과학교실UU0000951  ); 윤홍식   (영남대학교 의과대학 치과학교실UU0000951  ); 진병로   (영남대학교 의과대학 치과학교실UU0000951  ); 백석환   (영남대학교 의과대학 생화학.분자생물학교실UU0000951  );
  • 초록

    Background: Phosphatidic acid(PA), an important second messenger, is involved in inflammation. Notably, cell-cell interactions via adhesion molecules playa central role in inflammation. This thesis show that PA induces expression of intercellular adhesion molecule-1(ICAM-1) on macrophages and describe the signaling pathways. Materials and methods: Macrophages were cultured in the presence of 10% FBS and assayed cell to cell adhesion using HUVEC. For the gene and protein analysis, RT-PCR, Western blot and flow cytometry were performed. In addition, overexpressed cell lines for dominant negative PKC- ${\delta}$ mutant established and tested their effect on the promoter activity and expression of ICAM-1 protein by PA. Results: PA-activated macrophages significantly increased adhering to human umbilical vein endothelial cell and this adhesion was mediated by ICAM-1. Pretreatment with rottlerin(PKC- ${\delta}$ inhibitor) or expression of a dominant negative PKC- ${\delta}$ mutant, but not Go6976(classical PKC- ${\alpha}$ inhibitor) and myristoylated PKC- ${\xi}$ inhibitor, attenuated PA-induced ICAM-1 expression. The p38 mitogen-activated protein kinase(MAPK) inhibitor blocked PA-induced ICAM-1 expression in contrast, ERK upstream inhibitor didn't block ICAM-1. Conclusion: These data suggest that PA-induced ICAM-1 expression and cell-cell adhesion in macrophages requires PKC- ${\delta}$ activation and that PKC- ${\delta}$ activation is triggers to sequential activation of p38 MAPK.


  • 주제어

    Macrophage .   ICAM-1 .   Adhesion .   MAPK .   Protein kinase C.  

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