Open AccessHuman herpes virus 8 interleukin‐6 homologue triggers gp130 on neuronal and hematopoietic cells
Author(s) -
Hoischen Susanne H.,
Vollmer Petra,
März Pia,
Özbek Suat,
Götze Katharina S.,
Peschel Christian,
Jostock Thomas,
Geib Till,
Müllberg Jürgen,
Mechtersheimer Sabine,
Fischer Martina,
Grötzinger Joachim,
Galle Peter R.,
RoseJohn Stefan
Publication year - 2000
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2000.01389.x
Subject(s) - fusion protein , glycoprotein 130 , biology , cytokine , microbiology and biotechnology , recombinant dna , cancer research , interleukin 6 , immunology , biochemistry , gene
Human herpes virus‐8 (HHV8) encodes a cytokine named viral interleukin‐6 (vIL‐6) that shares 25% amino‐acid identity with its human homologue. Human IL‐6 is known to be a growth and differentiation factor of lymphatic cells and plays a potential role in the pathophysiology of various lymphoproliferative diseases. vIL‐6 is expressed in HHV8‐associated‐diseases including Kaposi's sarcoma, Body‐cavity‐based‐lymphoma and Castleman's disease, suggesting a pathogenetic involvement in the malignant growth of B‐cell associated diseases and other malignant tumours. We expressed vIL‐6 in Escherichia coli as a fusion protein with recombinant periplasmic maltose binding protein. After cleavage from the maltose binding protein moiety and purification, vIL‐6 was shown to be correctly folded using circular dichroism spectroscopy. A rabbit antiserum was raised against the recombinant vIL‐6 protein. vIL‐6 turned out to be active on cells that expressed gp130 but no IL‐6 receptor (IL‐6‐R) suggesting that, in contrast to human IL‐6, vIL‐6 stimulated gp130 directly. Accordingly, vIL‐6 activity could be inhibited by a soluble gp130 Fc Fusion protein. vIL‐6 was shown to induce neuronal differentiation of rat pheochromocytoma cells and to stimulate colony formation of human hematopoietic progenitor cells. Thus, vIL‐6 exhibits biologic activity that has only been observed for the IL‐6/soluble IL‐6‐R complex but not for IL‐6 alone. These properties are important for the evaluation of the pathophysiological potential of vIL‐6.