Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells

被引:34
作者
Klouche, M
Brockmeyer, N
Knabbe, C
Rose-John, S
机构
[1] Robert Bosch Krankenhaus, Dept Lab Med, Inst Clin Pathol, D-70376 Stuttgart, Germany
[2] Robert Bosch Soc Med Res, Stuttgart, Germany
[3] Ruhr Univ Bochum, Dept Dermatol, D-4630 Bochum, Germany
[4] Univ Kiel, Inst Biochem, D-2300 Kiel, Germany
关键词
AIDS; HHV8; Kaposi's sarcoma; KS-associated herpesvirus; PTX3; vIL-6;
D O I
10.1097/00002030-200205240-00001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: 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. Design: Proinflammatory activation of KS cells was compared using vIL-6, human IL6, 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. Methods: 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. Results: 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. Conclusion: 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. (C) 2002 Lippincott Williams Wilkins.
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页码:F9 / F18
页数:10
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