Rosiglitazone activation of PPARgamma suppresses fractalkine signaling.
Rosiglitazone activation of PPARgamma suppresses fractalkine signaling.
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DOI：
10.1677/jme-09-0090
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发表时间：
2010-02
影响因子：
3.5
通讯作者：
Evans RM
中科院分区：
文献类型：
--
作者：
Wan Y;Evans RM
核受体过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ，PPARγ）是脂质代谢和炎症的关键转录调节因子。合成的PPARγ激动剂噻唑烷二酮类（如罗格列酮）作为胰岛素抵抗和II型糖尿病药物的广泛使用，突出了PPARγ的重要性。Fractalkine（FKN）及其受体（FR）通过调节白细胞迁移和粘附到炎症外周组织中，在免疫应答中发挥重要作用。在这项研究中，我们已经确定了一个新的联系之间的过氧化物酶体增殖物激活受体γ激活和FKN信号。一方面，罗格列酮激活巨噬细胞中的PPARγ，不仅抑制FR基因的转录，而且阻止FR蛋白的质膜转位。另一方面，罗格列酮激活内皮细胞中的PPARγ也阻碍了FKN的核输出。总之，这些数据表明，PPARγ激活抑制FKN信号传导。这些发现表明了一种以前未被认识到的机制，可能有助于PPARγ的抗炎作用。
The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a key transcriptional regulator of both lipid metabolism and inflammation. The importance of PPARγ is accentuated by the widespread use of synthetic PPARγ agonists, thiazolidinediones (such as rosiglitazone), as drugs for insulin resistance and type II diabetes. Fractalkine (FKN) and FKN receptor (FR) play an important role in the immune responses by regulating leukocyte migration and adhesion to inflamed peripheral tissues. In this study, we have identified a novel link between PPARγ activation and FKN signaling. On one hand, the activation of PPARγ by rosiglitazone in macrophages not only represses the transcription of the FR gene, but also prevents the plasma membrane translocation of the FR protein. On the other hand, the activation of PPARγ by rosiglitazone in endothelial cells also impedes the nuclear export of FKN. Together, these data suggest that PPARγ activation represses FKN signaling. These findings indicate a previously unrecognized mechanism that may contribute to the anti-inflammatory effect of PPARγ.