Klouche Mariam, Brockmeyer Norbert, Knabbe Cornelius, Rose-John Stefan
Institute of Clinical Pathology, Department of Laboratory Medicine, Robert Bosch Hospital and Robert Bosch Society for Medical Research, Stuttgart, Germany.
AIDS. 2002 May 24;16(8):F9-18. doi: 10.1097/00002030-200205240-00001.
To analyse if human herpesvirus 8 (HHV8)-derived viral interleukin-6 (vIL-6) has the capacity to activate Kaposi's sarcoma (KS) cells to elicit a local acute-phase response.
Proinflammatory activation of KS cells was compared using vIL-6, human IL-6, as well as the complex of human IL-6 with the soluble IL-6 receptor, and expression of the novel acute-phase protein pentraxin-3 (PTX3) was analysed.
We established primary KS cell cultures from patients with AIDS-associated and classical KS and expressed recombinant HHV8-derived vIL-6 in COS-7 cells. Expression of PTX3 by vIL-6-stimulated KS cell cultures was analysed by quantitative real-time reverse transcriptase-polymerase chain reaction. Mitogenic effects of vIL-6 on the KS cells of distinct aetiology were compared by [3H]thymidine incorporation.
We show that vIL-6 induced a marked and sustained expression of the novel acute-phase protein PTX3 in human primary KS cell cultures. vIL-6 directly activated KS cells, which uniquely expressed gp130, the signal-transducing subunit of the IL-6 receptor, but were negative for the IL-6-binding unit (IL-6R). In contrast, human IL-6 did not stimulate KS cells in the absence of the full IL-6R. Expression of PTX3 messenger RNA increased by more than 25-fold in vIL-6-stimulated KS cells after 24 h. Particularly after extended incubation with the virokine, vIL-6 mediated a pronounced mitogenic effect on KS cells.
The induction of an extrahepatic acute-phase response by vIL-6-activated KS cells may contribute to local tissue damage and the attraction of inflammatory cells, and add to a more aggressive phenotype.
分析人疱疹病毒8型（HHV8）衍生的病毒白细胞介素-6（vIL-6）是否有能力激活卡波西肉瘤（KS）细胞以引发局部急性期反应。
使用vIL-6、人白细胞介素-6以及人白细胞介素-6与可溶性白细胞介素-6受体的复合物比较KS细胞的促炎激活，并分析新型急性期蛋白五聚素-3（PTX3）的表达。
我们从艾滋病相关型和经典型KS患者中建立了原代KS细胞培养物，并在COS-7细胞中表达重组HHV8衍生的vIL-6。通过定量实时逆转录聚合酶链反应分析vIL-6刺激的KS细胞培养物中PTX3的表达。通过[3H]胸苷掺入比较vIL-6对不同病因的KS细胞的促有丝分裂作用。
我们表明，vIL-6在人原代KS细胞培养物中诱导了新型急性期蛋白PTX3的显著且持续的表达。vIL-6直接激活KS细胞，这些细胞独特地表达gp130，即白细胞介素-6受体的信号转导亚基，但白细胞介素-6结合单位（IL-6R）呈阴性。相比之下，在没有完整白细胞介素-6受体的情况下，人白细胞介素-6不会刺激KS细胞。24小时后，vIL-6刺激的KS细胞中PTX3信使核糖核酸的表达增加了25倍以上。特别是在与这种病毒因子长时间孵育后，vIL-6对KS细胞介导了明显的促有丝分裂作用。
vIL-6激活的KS细胞诱导肝外急性期反应可能导致局部组织损伤和炎症细胞的吸引，并加重更具侵袭性的表型。
