Interferon γ-inducible protein 10 selectively inhibits proliferation and induces apoptosis in endothelial cells
Interferon γ-inducible protein 10 selectively inhibits proliferation and induces apoptosis in endothelial cells
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DOI：
10.1245/aso.2006.03.038
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
Alexander, HR
中科院分区：
文献类型：
--
作者：
Feldman, ED;Weinreich, DM;Alexander, HR
背景：干扰素γ诱导蛋白10（IP-10）在多种小鼠模型中具有抗肿瘤作用。IP-10受体有两个不同的剪接变异体，CXCR 3A和CXCR 3B，有矛盾的影响后，配体-受体interaction.Methods：为了表征IP-10的推定的抗血管生成作用，我们测量了增殖率和凋亡的人脐静脉内皮细胞（HUVECs），成纤维细胞，A375黑色素瘤或WIDR腺癌细胞系暴露后的重组蛋白。CXCR3A（激活）和CXCR 3B（抑制/促凋亡）信使RNA（mRNA）的表达水平在成纤维细胞，2人肿瘤细胞系，T淋巴细胞，和HUVECs的不同细胞密度的characterized.Results：IP-10导致剂量依赖性和选择性抑制增殖和对抗血管内皮生长因子在HUVECs的增殖作用，但不影响成纤维细胞或2人肿瘤细胞系。此外，IP-10在HUVECS中导致有效和选择性的细胞凋亡诱导，但对成纤维细胞或A375黑素瘤没有影响。逆转录-聚合酶链反应显示，融合的HUVECs中CXCR 3B剪接变异体的mRNA占优势，HUVECs中CXCR 3B与CXCR 3A mRNA的比值> 40，而HUVECs中CXCR 3B与CXCR 3A mRNA的比值> 40。
Background: Interferon gamma-oinducible protein 10 (IP-10) has antitumor effects in various murine models. The IP-10 receptor has two distinct splice variants, CXCR3A and CXCR3B, that have paradoxical effects after ligand-receptor interaction.Methods: To characterize the putative antiangiogenic effects of IP-10, we measured proliferation rates and apoptosis in human umbilical vein endothelial cells (HUVECs), fibroblasts, and A375 melanoma or WIDR adenocarcinoma cell lines after exposure to the recombinant protein. CXCR3A (activating) and CXCR3B (inhibitory/proapoptotic) messenger RNA (mRNA) expression levels in fibroblasts, 2 human tumor cell lines, T lymphocytes, and HUVECs of varying cell densities were characterized.Results: IP-10 resulted in dose-dependent and selective inhibition of proliferation and countered the proliferative effects of vascular endothelial growth factor in HUVECs but did not affect fibroblasts or 2 human tumor cell lines. In addition, IP-10 resulted in potent and selective induction of apoptosis in HUVECS but had no effect on fibroblasts or A375 melanoma. Confluent HUVECs had a predominance of mRNA for the CXCR3B splice variant by reverse transcriptase-polymerase chain reaction, and the ratio of CXCR3B to CXCR3A mRNA was > 40 in HUVECs, compared with