Ticlopidine
抑制腫瘤壞死因子 -α 刺激人類臍帶內皮細胞所分泌的單核球趨化激素 -1 與介 白質素 -8 之探討Ticlopidine Inhibits Monocyte Chemoattractant Protein-1 and Interleukin-8 Expression in TNF--α Stimulated Human Umbilical Vein Endothelial Cells
Ticlopidine 抑制腫瘤壞死因子 -α 刺激人類臍帶內皮細胞所分泌的 單核球趨化激素 -1 與介白質素 -8 之探討
戴子怡動脈硬化是一種發炎性的疾病會影響人類的健康，當動脈管壁上的內皮細胞 層受到損傷時會導致血液中的單核球及 T- 淋巴球匯集至血管管壁內是為動脈 硬化初期發展過程的主要特徵之一，而趨化素為單核球及 T- 淋巴球遷移作用 的調控者其中就包括有單核球趨化素 -1; 單核球趨化素 -1 會表現在動脈硬化 損傷部位內而導致單核球與 T- 淋巴球過量地聚集，而 IL-8 在過去有研究指出 在動脈硬化損傷部位內有 IL-8 的存在以及從動脈硬化的患者體內分離出來的 巨噬細胞會表現 IL-8 。 ticlopidine 是一種抗血栓的藥物可用來預防治療動脈 硬化，但是有關於 ticlopidine 的作用機制尚未清楚地了解。
在本研究中我們主要探討 ticlopidine 對於受到 TNF-α 刺激的 HUVEC 所表現 的單核球趨化素 -1 (MCP-1) 和介白質素 -8 (IL-8) 之影響。結果顯示 ticlopidin e 可抑制 TNF-α 所誘導 MCP-1 和 IL-8 的蛋白質及 mRNA 表現，亦可抑制 T NF-α 所誘導 VCAM-1 的表現。同時 Ticlopidine 可抑制 U937 單核球的吸附 作用。加入抗 MCP-1 及抗 IL-8 抗體都可抑制單核球的吸附作用。此外我們也 發現到在 U937 上有 IL-8 receptor CXCR1 的存在，而 IL-8 對於 U937 具有趨 化性的作用。這些結果顯示 ticlopidine 可抑制受到 TNF-α 刺激的 HUVEC 表 現 MCP-1 、 IL-8 及 VCAM-1 ，為此可能提供了另一項治療機制。
Ticlopidine Inhibits Monocyte Chemoattractant Protein-1 and Interleukin-8 Expression in TN F-α Stimulated
Human Umbilical Vein Endothelial Cells Tzu-Yi Tai
Atherosclerosis is an inflammatory disease, it can influence human ， s heath . Key evidence of atherosclerosis is the initial influx of monocytes and T-lymphocytes into the vessel wall in r esponse to injury to the endothelium. Mediators of this migration are chemokines including m onocyte chemoattractant protein-1 (MCP-1). MCP-1 were expressed in human atherosclerotic lesions, cause monocytes 、 T-lymphocyte into the subendothelial space and lead over collecti on. IL-8 has been reported in atherosclerotic lesions and circulating macrophages from patient s with atherosclerosis. Ticlopidine is an antithrombotic agent which used to prevent atheroscle rosis, but its mechanism of action has not yet been completely understood. In this study, the ef fects of ticlopidine on MCP-1 and IL-8 expression in TNF-α stimulated human umbilical vein endothelial cells (HUVECs) were investigated.
We have demonstrated ticlopidine inhibits TNF-α-induced MCP-1 and IL-8 protein and mRN A expression. Ticlopidine inhibits TNF-α-induced VCAM-1 expression. Ticlopidine also inhi bits U937 monocytic cell to adhere to HUVECs, the treatment of anti IL-8 and anti MCP-1 ant ibodies inhibit monocytes adhesion. Besides, we found IL-8 receptor CXCR1 were expressed on U937 cells, and U937 respond chemotactically to CXC chemokine IL-8 in vitro. These resu lts suggest that ticlopidine inhibits MCP-1 、 IL-8 and VCAM-1 expression in HUVEC stimul ated by TNF-α, thereby providing an additional mechanism for therapeutic effect of ticlopidin e.
