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인간의 Jurkat T세포에서 프로스타글란딘 PGE2) (PGE2)의 cAMP 경로를 통한 인터페론 감마(INF--γ ) 유전자의 methylation

PGE2 Mediated INF-γ Gene Methylation Through cAMP Signaling Pathway in Human Jurkat T Cells

  • 전병훈 (원광대학교 한의과대학) ;
  • 주성민 (원광대학교 한의과대학) ;
  • 정재성 (원광대학교 한의과대학) ;
  • 김명완 (원광대학교 한의과대학) ;
  • 윤용갑 (원광대학교 한의과대학) ;
  • 박현 (원광대학교 의과대학) ;
  • 정헌택 (원광대학교 의과대학) ;
  • 한동민 (원광대 자연대학 생명과학부) ;
  • 김원신 (원광대 자연대학 생명과학부)
  • Jeon, Byung-Hun (College of Oriental Medicine, Wonkwang University) ;
  • Ju, Sung-Min (College of Oriental Medicine, Wonkwang University) ;
  • Jeong, Jae-Sung (College of Oriental Medicine, Wonkwang University) ;
  • Kim, Myung-Wan (College of Oriental Medicine, Wonkwang University) ;
  • Yun, Young-Gab (College of Oriental Medicine, Wonkwang University) ;
  • Park, Hyun (School of Medicine & Medical Resources Research Center, Wonkwang University) ;
  • Chung Hun-taeg (School of Medicine & Medical Resources Research Center, Wonkwang University) ;
  • Han, Dong-Min (College of Natural Sciences and Institute of Basic Natural Sciences, Wonkwang University) ;
  • Kim, Won-Sin (College of Natural Sciences and Institute of Basic Natural Sciences, Wonkwang University)
  • 발행 : 2004.08.01

초록

본 연구에서 인간의 백혈병세포주인 Jurkat T 세포에서 인터페론 감마(INF-${\gamma}$ 유전자의 methylation에 대한 S-nitroso-N-acetylpenicillamine (SNAP), 프로스타글란딘 $E_2$ (PG $E_2$) 그리고 dibutric cyclic AMP (dbcAMP)의 효과를 조사하였다. 인터페론 감마 유전자의 프로모터기능에 아주 중요한 디뉴클레오티드인 CpG는 SNAP, PG $E_2$, 그리고 dbcAMP를 각각 처리하였을 때 methylation되었다. PG $E_2$에 의해서 유도된 그 methylation은 아데닐산 사이클라제의 저해제의 하나인 2',5'-dideoxyadenosine (DDA)에 의해서 억제되었지만, SNAP에 의해서 유도된 methylation은 DDA에 의해서 억제되지 않았다. PG $E_2$나 dbcAMP를 처리한 세포에서 일산화질소(NO)의 생성의 증가는 나타나지 않았으며, PG $E_2$나 dbcAMP에 의해 유도된 인터페론 감마유전자의 methylation도 일산화질소합 성효소의 저해제인 $N^{G}$ -methyl-L-arginine (L-NMMA)에 의해서 억제되지 않았다. 따라서 인간의 Jurkat T 세포에서 PG $E_2$에 의한 인터페론 감마 유전자의 발현 억제는 세포내의 cAMP생성경로를 통한 인터페론 감마 유전자의 methylation과 연관되어있으나 일산화질소의 생성경로와는 무관한 것으로 보인다.화질소의 생성경로와는 무관한 것으로 보인다.

We have examined the effects of S-nitroso-N-acetylpenicillamine (SNAP), prostaglandin $E_2$ (PG $E_2$) and dibutric cyclic AMP (dbcAMP) on the methylation of interferon- ${\gamma}$ (IFN- ${\gamma}$ ) gene in human Jurkat T cells. The CpG dinucleotide which is critical for promoter function of IFN- ${\gamma}$ gene was methylated by treatment with SNAP, PG $E_2$ and dbcAMP, respectively. The DNA methylation induced by PG $E_2$ was suppressed by the addition of 2',5'-dideoxyadenosine (DDA), an inhibitor of adenylyl cyclase, but the suppression was not observed in SNAP treated cells. The NO production was not enhanced in PG $E_2$ or dbcAMP treated cells. The methylation induced by PG $E_2$ and dbcAMP was not suppressed by the addition of $N^{G}$-methyl-L-arginine (L-NMMA), NO synthase inhibitor. In conclusion, the inhibition of INF- ${\gamma}$ gene expression by PG $E_2$ was associated with the methylation of INF- ${\gamma}$ gene by elevation of intracellular cAMP in human Jurkat T cells. However, the methylation induced by PG $E_2$ might not be mediated through the NO production.rough the NO production.

키워드

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