Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells.
Seroepidemiology and polymerase chain reaction studies have strongly suggested that human herpesvirus type 8 (HHV-8) is associated with Kaposi's sarcoma, Castleman's disease, and body cavity-based lymphoma. The genome of HHV-8 harbors a viral analogue of the interleukin-6 (IL-6) gene. The amino acid sequence of the viral IL-6 (vIL-6) protein is 24.7% identical to human IL-6 (hIL-6). IL-6 as a B-cell growth and differentiation factor is known to play an essential role in the pathophysiology of B-cell tumors. Thus, it seems possible that virus-encoded IL-6 contributes to malignant growth of HHV-8-positive B-cell lymphatic tumors. We have tested a preparation of HHV-8-derived IL-6 for the ability to promote the proliferation of the human myeloma cell line INA-6, which is strictly dependent on exogenous IL-6 for growth and survival. Viral IL-6 significantly induced DNA synthesis of INA-6 cells, but required much more protein on a weight basis when compared with hIL-6 for maximal proliferation. The proliferative effect of vIL-6 was almost completely inhibited by a combination of anti-IL-6 receptor (IL-6R) and anti-gp130 antibodies or IL-6R superantagonist Sant7 and anti-gp130 antibodies. This report demonstrates that vIL-6 has proliferative activity on human cells and that the IL-6R and gp130 are involved in vIL-6 signaling in the myeloma cell line INA-6.
Burger
R
R
Division of Hematology/Oncology, Department of Medicine III, the Institute for Clinical and Molecular Virology, University of Erlangen-Nuernberg, Erlangen, Germany.
Neipel
F
F
Fleckenstein
B
B
Savino
R
R
Ciliberto
G
G
Kalden
J R
JR
Gramatzki
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D050822:Cytokine Receptor gp130; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology; D009101:Multiple Myeloma / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004273:DNA, Neoplasm; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014764:Viral Proteins; D050822:Cytokine Receptor gp130