Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas
Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas
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DOI：
10.1016/s0002-9440(10)63921-1
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发表时间：
2003-04-01
影响因子：
6
通讯作者：
Mukaida, N
中科院分区：
文献类型：
--
作者：
Lu, PR;Nakamoto, Y;Mukaida, N
肝癌细胞系能产生大量的趋化因子，对包括肝炎病毒及其产物在内的各种刺激做出反应。然而，关于趋化因子受体(S)在肝癌组织中的表达类型及其在肝癌发生发展中的作用，目前尚不清楚。为了阐明这一点，我们检测了六个人肝癌细胞系中趋化因子受体的表达。所有肝癌细胞系的细胞表面都有CCR1mRNA及其蛋白的组成性和专一性表达。CCR1在肝癌细胞上也有表达，在肝癌组织内皮细胞也有表达，而在正常肝组织中未见表达。此外，CCL3在肝癌组织中的癌细胞、内皮细胞和成纤维细胞样细胞中均有表达，而在正常肝组织中仅偶见血管内皮细胞和炎性细胞呈弱阳性。此外，CCR1、CCL3、CCL4和CCL5的配体抑制了Forsklin介导的细胞内cAMP浓度的升高，表明表达的CCR1是有功能的。4株肝癌细胞株仅对IL-1α和IL-1β反应产生CCL3。IL-1α和IL-1β在肝癌组织中大量表达，而在正常肝组织中不表达。因此，IL-1可能以自分泌和/或旁分泌的方式促进局部CCL3的产生，CCL3可能与肝癌细胞上表达的CCR1相互作用。
Hepatoma cell lines can produce a massive amount of chemokines in response to various stimuli including hepatitis viruses and their products. However, it remains elusive on the types of chemokine receptor(s) expressed in the hepatoma tissues and its roles in hepatoma development. To clarify these points, we examined the chemokine receptor expression in six human hepatoma cell lines. All of the hepatoma cell lines constitutively and exclusively expressed CCR1 mRNA and its protein on their cell surface. CCR1 expression was also detected on hepatoma cells and to a lesser degree, on endothelial cells in hepatoma tissues but not in normal liver tissues. Furthermore, CCL3 expression was detected in hepatoma cells, endothelial cells, and to a lesser degree, fibroblast-like cells in hepatoma tissue, whereas only occasional vascular endothelial cells and inflammatory cells in normal liver tissues were weakly positive for CCL3. Moreover, the forskolin-mediated increases in intracellular cAMP concentrations were inhibited by the ligands for CCR1, CCL3, CCL4, and CCL5, suggesting that the expressed CCR1 was functional. Four hepatoma cell lines produced CCL3 only in response to interleukin (IL)-1alpha and IL-1beta. Finally, IL-1alpha and IL-1beta were detected abundantly in hepatoma tissues but not in normal liver tissues. Thus, IL-1 may enhance the local production of CCL3, which may interact with CCR1 expressed on hepatoma cells, in an autocrine and/or paracrine manner.