펩티도글라이칸에 의한 인터루킨-1 베타 발현 기전 연구

Abstract

본 연구에서는 IL-<TEX>$1{\beta}$</TEX> 발현에 PG의 영향을 조사하였고, 단핵세포에서 PG에 의한 IL-<TEX>$1{\beta}$</TEX> 상향조절에 포함된 세포인자를 밝혔다. PG에 사람의 THP-1 세포를 노출시키면 IL-<TEX>$1{\beta}$</TEX> 분비 증가뿐만 아니라 IL-<TEX>$1{\beta}$</TEX> 유전자 전사를 유도하는 결과를 가져왔고, TLR-2/4의 억제제인 OxPAPC에 의해 저해되었다. U0126, SP6001250, Akti IV, rapamycin, DPI 같은 약리학적 저해제도 PG에 의한 IL-<TEX>$1{\beta}$</TEX>의 상향조절을 상당히 약화시켰다. 그러나 polymyxin B는 IL-<TEX>$1{\beta}$</TEX> 발현에 영향을 미치지 않았다. 본 연구는 PG는 TLR-2, Akt, mTOR, MAPKs, ROS를 통하여 IL-<TEX>$1{\beta}$</TEX>의 발현을 상향시킴을 확인하였다. This study investigated the effects of PG on IL-<TEX>$1{\beta}$</TEX> expression and determined cellular factors involved in PG-mediated IL-<TEX>$1{\beta}$</TEX> 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-<TEX>$1{\beta}$</TEX> and also profound induction of the IL-<TEX>$1{\beta}$</TEX> 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-<TEX>$1{\beta}$</TEX> up-regulation. However, polymyxin B did not influence the IL-<TEX>$1{\beta}$</TEX> expression. This study indicates that PG contributes to vascular inflammation in atherosclerotic plaques by up-regulating expression of IL-<TEX>$1{\beta}$</TEX> via TLR-2, Akt, mTOR, MAPKs, and ROS.