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


METHODS
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.


CONCLUSIONS
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.
Klouche
Mariam
M
Institute of Clinical Pathology, Department of Laboratory Medicine, Robert Bosch Hospital and Robert Bosch Society for Medical Research, Stuttgart, Germany. mariam.klouche@rbk.de
Brockmeyer
Norbert
N
Knabbe
Cornelius
C
Rose-John
Stefan
S
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000210:Acute-Phase Reaction; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002097:C-Reactive Protein / Q000096:biosynthesis*; D019556:COS Cells; D002455:Cell Division; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000502:physiology*; D000099153:Pentraxins
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D002097:C-Reactive Protein; D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D014764:Viral Proteins; D000099153:Pentraxins; C494199:IL6ST protein, human