Inhibition of GROalpha-induced human endothelial cell proliferation by the alpha-chemokine inhibitor antileukinate.
Inhibition of GROalpha-induced human endothelial cell proliferation by the alpha-chemokine inhibitor antileukinate.
复制标题
α-趋化因子抑制剂抗白细胞介素抑制 GROα 诱导的人内皮细胞增殖。
DOI：
10.1006/cyto.1998.0418
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Miller,EJ
中科院分区：
文献类型：
--
作者：
Fujisawa,N;Hayashi,S;Kurdowska,A;Carr,FK;Miller,EJ
GROαan autocrine mitogenic factor for melanoma cell lines, belongs to the superfamily of α-chemokines. Here, we report that GROα stimulates the growth of human umbilical vein endothelial cells (HUVEC) in vitro, with proliferation being significantly stimulated by 100nM recombinant human (rh) GROαProliferation was significantly inhibited by 100μg/ml anti- human GROα monoclonal antibody (mAb), while excess GROα restored the growth. The addition of rhIL-8, rhIP-10, anti-human IL-8 or anti-human ENA-78 mAbs did not alter HUVEC proliferation. [125I]IL-8 binding to HUVEC was saturable and inhibited by non-radioactively iodinated IL-8, but not non-iodinated IL-8. [125I]GROα binding was also inhibited by iodinated IL-8. Since these data suggested specific binding sites for α-chemokines on HUVEC, we tested the effect of antileukinate, a potent α-chemokine receptor inhibitor, on [125I]GROα binding. Antileukinate inhibited GROα binding and suppressed HUVEC proliferation in a dose-dependent manner. Antileukinate was not cytotoxic, with no decrease in cell viability in the presence of 100μM antileukinate. These findings suggest that GROα is essential for HUVEC growth factor and that antileukinate inhibits growth by preventing autocrine GROα receptor binding. This raises the interesting possibility of α-chemokine receptor inhibitors, such as antileukinate, in the treatment of cancer where angiogenesis is an important factor for tumour growth.
