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3T3-L1 지방전구세포에서 합토글로빈에 의한 염증성 cytokine 발현 조절

The Effect of Haptoglobin on Expression of Inflammatory Cytokines in 3T3-L1 Preadipocytes.

  • 조진경 (가톨릭대학교 의과대학 자연과학교실) ;
  • 김남훈 (가톨릭대학교 의과대학 자연과학교실) ;
  • 오미경 (가톨릭대학교 의과대학 자연과학교실) ;
  • 박선주 (가톨릭대학교 의과대학 자연과학교실) ;
  • 김인숙 (가톨릭대학교 의과대학 자연과학교실)
  • Cho, Jin-Kyung (Department of Natural Sciences, College of Medicine, The Catholic University) ;
  • Kim, Nam-Hoon (Department of Natural Sciences, College of Medicine, The Catholic University) ;
  • Oh, Mi-Kyung (Department of Natural Sciences, College of Medicine, The Catholic University) ;
  • Park, Seon-Joo (Department of Natural Sciences, College of Medicine, The Catholic University) ;
  • Kim, In-Sook (Department of Natural Sciences, College of Medicine, The Catholic University)
  • 발행 : 2008.04.30

초록

백색지방조직(white adipose tissue)은 에너지 저장뿐만 아니라 다양한 adipokines을 분비하는 중요한 내분비 기관이다. 급성기반응 단백질로 알려져 있는 합토글로빈(haptoglobin)도 adipokine의 한 종류로서 지방세포에서 합성되고 분비된다. 그러나 adipokine으로서의 기능과 지방조직에서의 역할은 아직까지 규명되지 않았다. 본 연구에서는 3T3-L1 지방전구세포를 합토글로빈 유전자로 transfection 시켜 합토글로빈을 과발현하는 세포를 만들고 세포증식, 염증관련 인자들의 발현조절 및 단구세포의 유인성을 조사하였다. 그 결과, 합토글로빈은 3T3-L1 세포의 성장에는 별 영향을 미치지 않았으나 IL-6와 COX-2 발현을 저해하고 HO-1 합성을 증가하였다. 또한 THP-1 단구세포를 이용한 invasion assay에서는 합토글로빈이 단구세포의 이동을 저해하였다. 이러한 결과들은 합토글로빈이 지방조직에서 항염증 반응에 관여함을 시사한다. 만성적 염증상태(chronic low-grade inflammatory state)로 인식되고 있는 비만은 염증관련 인자들에 의한 인슐린저항성이 유도되는 바, 합토글로빈은 비만 관련 인슐린저항성을 방지하고 인슐린민감성을 향상시키는 데에도 기여할 것으로 생각된다.

White adipose tissue is now recognized as an important endocrine organ which secretes various signal factors and proteins termed 'adipokine'. Haptoglobin (Hp), which has been known as an acute phase protein, belongs to the adipokine. However, the function of Hp in adipose tissue remains unclear. To verify the role of Hp in preadipocytes, in this study, 3T3-L1 preadipocyte cells were stably transfected with human Hp gene and Hp-overexpressing cells were made. The Hp had no effect on cell growth of preadipocytes. By RT-PCR and Western blot analysis, the Hp inhibited gene expression of IL-6 and COX-2 and enhanced HO-1 synthesis in preadipocytes. Moreover, invasion assay showed the Hp suppressed migration of monocytes to preadipocytes. These findings suggest that the Hp may inhibit an inflammatory reaction in adipose tissue by regulating the expressions of pro-inflammatory and anti-inflammatory mediators, and by repressing monocytes/macrophages infiltration.

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