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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 |
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| Authors: | Murakami-Morl Kaoru; Taga Tetsuya; Kishimoto Tadamitsu; Nakamura Shuji |
| Institution: | 1 Institute of Molecular Medicine, Huntington Memorial Hospital Pasadena, CA 91105, USA 2 Department of Medicine, University of Southern California Los Angeles, CA 90033, USA 3 Institute for Molecular and Cellular Biology, Osaka University Suita, Osaka 565, Japan 4 Department of Medicine III, Osaka University Medical School Suita, Osaka 565, Japan |
| Abstract: | Kaposi's sarcoma (KS) is most frequently associated with HIV-intectedindividuals (AIDS-KS). While AIDS-KS-derived spindle cells (AIDS-KScells) contribute to the development of KS lesions, growth regulationof these cells in vivo is poorly understood. AIDS-KS cells expressconsiderable amounts of the signal transducing subunit (gp130)of the IL-6 receptor, but only a scanty amount of its bindingsubunit (IL-6R ). This phenotype can account for the lack ofIL-6 responsiveness of AIDS-KS cells. We now report that thesoluble form of IL-6R (sIL-6R), lacking transmembrane and cytopiasmicregions, functions as a potent growth factor for AIDS-KS cellsby making these cells responsive to IL-6. After exposure tosIL-6R together with lL-6 in culture, AIDS-KS cells assumeda spindle-shaped morphology and showed a remarkable augmentationof growth, while IL-6 alone did not induce AIDS-KS cell growth.Even without the addition of IL-6, sIL-6R induced significantgrowth levels of AIDS-KS cells. Since AIDS-KS cells expresshigh levels of IL-6, it is likely that, in the presence of sIL-6R,these cells acquire an IL-6 autocrine growth loop. Anti-gp130antibodies blocked the action of sIL-6R on AIDS-KS cells; hence,we refer to sIL-6R as a gp130-related AIDS-KS cell growth factor.In contrast, the soluble form of gp130 (sgp130) had inhibitoryeffects on AIDS-KS cell growth, thereby suggesting that a complexregulatory system is involved in the modulation of the gp130-mediatedAIDS-KS cell growth. In recent years, soluble forms of IL-6Rand gp130 have been detected in the sera of healthy individualsand increased levels of sIL-6R as well as IL-6 have been notedin the sera of HIV-infected patients. It seems reasonable toassume that perturbed production of sIL-6R and sgp130 may playa crucial role in the development and regression of AIDS-KSlesions by directly acting on growth of KS cells through thegp130-mediated pathway. |
| Keywords: | autocrine growth loop binding subunit HIV infection signal transduction soluble receptor |
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