title: The soluble form of the IL-6 receptor (sIL-6R alpha) is a potent growth factor for AIDS-associated Kaposi's sarcoma (KS) cells; the soluble form of gp130 is antagonistic for sIL-6R alpha-induced AIDS-KS cell growth.
abstract: Kaposi's sarcoma (KS) is most frequently associated with HIV-infected individuals (AIDS-KS). While AIDS-KS-derived spindle cells (AIDS-KS cells) contribute to the development of KS lesions, growth regulation of these cells in vivo is poorly understood. AIDS-KS cells express considerable amounts of the signal transducing subunit (gp130) of the IL-6 receptor, but only a scanty amount of its binding subunit (IL-6R alpha). This phenotype can account for the lack of IL-6 responsiveness of AIDS-KS cells. We now report that the soluble form of IL-6R alpha (sIL-6R alpha), lacking transmembrane and cytoplasmic regions, functions as a potent growth factor for AIDS-KS cells by making these cells responsive to IL-6. After exposure to sIL-6R alpha together with IL-6 in culture, AIDS-KS cells assumed a spindle-shaped morphology and showed a remarkable augmentation of growth, while IL-6 alone did not induce AIDS-KS cell growth. Even without the addition of IL-6, sIL-6R alpha induced significant growth levels of AIDS-KS cells. Since AIDS-KS cells express high levels of IL-6, it is likely that, in the presence of sIL-6R alpha, these cells acquire an IL-6 autocrine growth loop. Anti-gp130 antibodies blocked the action of sIL-6R alpha on AIDS-KS cells; hence, we refer to sIL-6R alpha as a gp130-related AIDS-KS cell growth factor. In contrast, the soluble form of gp130 (sgp130) had inhibitory effects on AIDS-KS cell growth, thereby suggesting that a complex regulatory system is involved in the modulation of the gp130-mediated AIDS-KS cell growth. In recent years, soluble forms of IL-6R alpha and gp130 have been detected in the sera of healthy individuals and increased levels of sIL-6R alpha as well as IL-6 have been noted in the sera of HIV-infected patients. It seems reasonable to assume that perturbed production of sIL-6R alpha and sgp130 may play a crucial role in the development and regression of AIDS-KS lesions by directly acting on growth of KS cells through the gp130-mediated pathway.
authors.affiliation: Institute of Molecular Medicine, Huntington Memorial Hospital, Pasadena, CA 91105, USA.
authors.forename: K
authors.initials: K
authors.lastname: Murakami-Mori
authors.forename: T
authors.initials: T
authors.lastname: Taga
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D050822:Cytokine Receptor gp130; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D012514:Sarcoma, Kaposi / Q000737:chemistry* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006133:Growth Substances; C494199:IL6ST protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D050822:Cytokine Receptor gp130