Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Molecular Mechanisms through Which Peptidoglycan Induces IL-1β Expression in Monocytic Cells

펩티도글라이칸에 의한 인터루킨-1 베타 발현 기전 연구

  • Seo, Hyun-Cheol (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Sun-Mi (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Lee, Sae-A (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Rhim, Byung-Yong (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Koanhoi (Department of Pharmacology, Pusan National University School of Medicine)
  • 서현철 (부산대학교 의학전문대학원 약리학교실) ;
  • 김선미 (부산대학교 의학전문대학원 약리학교실) ;
  • 이새아 (부산대학교 의학전문대학원 약리학교실) ;
  • 임병용 (부산대학교 의학전문대학원 약리학교실) ;
  • 김관회 (부산대학교 의학전문대학원 약리학교실)
  • Received : 2012.10.16
  • Accepted : 2012.12.06
  • Published : 2012.12.30
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Abstract

This study investigated the effects of PG on IL-$1{\beta}$ expression and determined cellular factors involved in PG-mediated IL-$1{\beta}$ up-regulation in mononuclear cells in order to understand the molecular mechanisms underlying inflammatory responses associated with bacterial pathogen-associated molecular patterns in the diseased artery. Exposure of human monocytic leukemia THP-1 cells to PG resulted in enhanced secretion of IL-$1{\beta}$ and also profound induction of the IL-$1{\beta}$ gene transcript. These effects were abrogated by OxPAPC, an inhibitor of TLR-2/4. Pharmacological inhibitors such as U0126, SP6001250, Akti IV, rapamycin, and DPI also significantly attenuated PG-mediated IL-$1{\beta}$ up-regulation. However, polymyxin B did not influence the IL-$1{\beta}$ expression. This study indicates that PG contributes to vascular inflammation in atherosclerotic plaques by up-regulating expression of IL-$1{\beta}$ via TLR-2, Akt, mTOR, MAPKs, and ROS.

본 연구에서는 IL-$1{\beta}$ 발현에 PG의 영향을 조사하였고, 단핵세포에서 PG에 의한 IL-$1{\beta}$ 상향조절에 포함된 세포인자를 밝혔다. PG에 사람의 THP-1 세포를 노출시키면 IL-$1{\beta}$ 분비 증가뿐만 아니라 IL-$1{\beta}$ 유전자 전사를 유도하는 결과를 가져왔고, TLR-2/4의 억제제인 OxPAPC에 의해 저해되었다. U0126, SP6001250, Akti IV, rapamycin, DPI 같은 약리학적 저해제도 PG에 의한 IL-$1{\beta}$의 상향조절을 상당히 약화시켰다. 그러나 polymyxin B는 IL-$1{\beta}$ 발현에 영향을 미치지 않았다. 본 연구는 PG는 TLR-2, Akt, mTOR, MAPKs, ROS를 통하여 IL-$1{\beta}$의 발현을 상향시킴을 확인하였다.

Keywords

References

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