Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte-activating polypeptide II (EMAP-II)
Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte-activating polypeptide II (EMAP-II)
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DOI：
10.1006/cyto.2000.0687
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发表时间：
2000-07-01
期刊：
影响因子：
3.8
通讯作者：
Libutti, SK
中科院分区：
文献类型：
--
作者：
Berger, AC;Alexander, HR;Libutti, SK
内皮单核细胞激活多肽-II（EMAP-II）是已知在中性粒细胞和巨噬细胞趋化性和凋亡中具有作用的炎性细胞因子，其是使肿瘤脉管系统对全身性TNF的作用敏感的肿瘤源性细胞因子。为了深入了解EMAP-II使血管对TNF敏感的机制，我着重于其对TNF受体表达的影响。在人脐静脉内皮细胞（HUVEC）中，TNF-R1 mRNA与重组EMAP-II孵育后增加4倍。与培养基对照和低表达细胞系相比，来自已知产生高水平EMAP-II的细胞系的条件培养基上调TNF-R1但不上调TNF-R2达20倍;这种作用被抗EMP-II抗体阻断，重组EMAP-II上调TNF-R1表达约6倍。通过ELISA分析HUVEC裂解物显示TNF-R1的表达在2小时内增加; TNF-R2的表达不受重组EMAP-II的影响。最后，体内人类黑色素瘤的免疫组织化学显示，与低EMAP-II表达肿瘤相比，已知表达高水平EMAP-II的肿瘤的血管上TNF-R1染色增加。这些结果表明，EMAP-Ⅱ上调TNF-R1表达的内皮细胞在体外和体内，TNF-R1表达的诱导可能是EMAP-Ⅱ敏感肿瘤内皮细胞的TNF的影响，导致出血性坏死的机制。(C)北京大学出版社.
Endothelial monocyte activating polypeptide-II (EMAP-II) is an inflammatory cytokine known to have a role in neutrophil and macrophage chemotaxis and in apoptosis, It is a tumour-derived cytokine that sensitizes tumour vasculature to the effects of systemic TNF. In order to gain insight into the mechanism by which EMAP-II sensitizes vessels to TNF, me focused on its effects on TNF receptor expression. In human umbilical vein endothelial cells (HUVEC), TNF-R1 mRNA is increased four-fold following incubation with recombinant EMAP-II. Conditioned media from cell lines known to produce high levels of EMAP-II upregulated TNF-R1 but not TNF-R2 by up to twenty-fold compared to media controls and low expressing cell lines; this effect was blocked by anti-EMP-II antibody, Recombinant EMAP-II upregulated TNF-R1 expression by approximately six-fold. Analysis of HUVEC lysates by ELISA showed increased expression of TNF-R1 within 2 h; TNF-R2 expression was unaffected by recombinant EMAP-II. Finally, immunohistochemistry of human melanomas in vivo showed that TNF-R1 staining is increased on the vessels of rumours known to express high levels of EMAP-II compared to low EMAP-II expressing tumours. These results suggest that EMAP-II upregulates TNF-R1 expression by endothelial cells both in vitro and in vivo, This induction of TNF-R1 expression may be the mechanism by which EMAP-II sensitizes tumour endothelium to the effects of TNF leading to haemorrhagic necrosis. (C) 2000 Academic Press.