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 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. 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.
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, humanIL-6, as well as the complex of humanIL-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, humanIL-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.
Authors: Yan-Jin Zhang; Rheba S Bonaparte; Deendayal Patel; David A Stein; Patrick L Iversen Journal: Mol Cancer Ther Date: 2008-03 Impact factor: 6.261
Authors: Melanie M Brinkmann; Marcel Pietrek; Oliver Dittrich-Breiholz; Michael Kracht; Thomas F Schulz Journal: J Virol Date: 2006-10-18 Impact factor: 5.103
Authors: Lyubomir A Dourmishev; Assen L Dourmishev; Diana Palmeri; Robert A Schwartz; David M Lukac Journal: Microbiol Mol Biol Rev Date: 2003-06 Impact factor: 11.056