Interferon- (cid:1) Induces Fas Trafficking and Sensitization to Apoptosis in Vascular Smooth Muscle Cells via a PI3K- and Akt-Dependent Mechanism-猫眼课题宝

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血管平滑肌细胞（VSMC）凋亡发生在晚期动脉粥样硬化斑块中，可能导致斑块不稳定。VSMC表达死亡受体Fas，但对Fas诱导的凋亡具有相对抗性，部分原因是Fas的细胞内隔离。尽管斑块中存在的炎性细胞因子如干扰素（IFN）-（cid：1）可使VSMCs启动FasL诱导的死亡，但这种作用的机制尚不清楚。我们研究了Fas表达和FasL诱导的人VSMCs细胞凋亡对IFN-（cid：1）的反应。IFN-（cid：1）在24小时内诱导Fas运输至细胞表面，这一作用需要Jak 2/Stat 1活性。IFN-（cid：1）也刺激Akt活性，并且通过阻断PI 3 K、Akt或Jak-2抑制Fas运输和Stat 1活化。IFN-（cid：1）在体外使Fas诱导的细胞凋亡增加46（cid：2）8%（平均值（cid：2）SEM，P（cid：3）0.04），该事件可通过抑制PI 3 K、Akt或Jak-2而消除。IFN-（cid：1）还增加Fas诱导的

Vascular smooth muscle cell (VSMC) apoptosis occurs in advanced atherosclerotic plaques where it may contribute to plaque instability. VSMCs express the death receptor Fas but are relatively resistant to Fas-induced apoptosis due in part to the intracellular sequestration of Fas. Although inflammatory cytokines such as interferon (IFN)- (cid:1) present in plaques can prime VSMCs to FasL-induced death, the mechanism of this effect is un-clear. We examined Fas expression and FasL-induced apoptosis in human VSMCs in response to IFN- (cid:1) . IFN- (cid:1) induced Fas trafficking to the cell surface within 24 hours, an effect that required Jak2/Stat1 activity. IFN- (cid:1) also stimulated Akt activity, and both Fas trafficking and Stat1 activation were inhibited by blocking PI3K, Akt, or Jak-2. IFN- (cid:1) increased Fas-induced apoptosis in vitro by 46 (cid:2) 8% (mean (cid:2) SEM, P (cid:3) 0.04), an event that could be abrogated by inhibition of PI3K, Akt, or Jak-2. IFN- (cid:1) also increased Fas-induced

Interferon- (cid:1) Induces Fas Trafficking and Sensitization to Apoptosis in Vascular Smooth Muscle Cells via a PI3K- and Akt-Dependent Mechanism

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