EXPRESSION OF INTERLEUKIN-6 RECEPTORS AND NF-6B IN AIDS-RELATED KAPOSI SARCOMA CELL STRAINS

Abstract

AIDS-related Kaposi sarcoma (AIDS-KS) is the most common malignancy associated withHIV infection, with an incidence of 10-30% of all AIDS patients. As such, there have been alarge number of AIDS-KS cell strains isolated and numerous studies conducted to elucidate themechanisms of malignancy in this disease. We have reported histological grade associateddifferences in the ability of AIDS-KS cell strains to proliferate under conditions of minimalgrowth factor supplementation, with strains derived from high grade lesions having enhancedproliferation potential. Furthermore, we found that this difference in in vitro growthcharacteristics was not attributed to grade associated differences in autologous growth factorrelease. These current investigations explored the hypothesis that grade associated growthdifferences could be attributed to differences in the expression of the components of the IL-6receptor, or expression/inducibility of the pleotrophic transcription factor NF-6B. Wedetermined there were no significant grade associated differences in the expression of eithercomponent (IL-6R " chain or gpl30) of the IL-6 receptor. However, non-lesional oral derivedcell strain lysates from AIDS-KS patients (n=4) contained significantly lower concentrations ofboth components of the IL-6 receptor than AIDS-KS strains (n=8) and lower concentrations ofgp-130 than normal human oral derived fibroblasts (n=2). Comparative analysis of seraconcentrations of soluble components of the IL-6 receptor did not demonstrate significantdifferences between HIV+/KS+(n=7), HIV+/KS-(n=9) and normal (HIV-/KS-) (n=4)populations. Further, no differences were detected in the expression of NF-6B in AIDS-KS cellstrains (n=5) derived from both high and low histological grade lesions as compared tonon-lesional AIDS-KS cell stain (n= 1) and normal human oral derived fibroblasts (n=2) underconditions of: constitutive/proliferative growth, sera starvation, oxidative stress, and mitogenreintroduction after sera starvation. In conclusion, these investigations have eliminated twoexplanations for histological grade associated differences for in vitro growth potential of AIDSrelated KS cell strains and further substantiated the lack of systemic paracrine cytokine/cytokinereceptor effects in AIDS-KS pathogenesis.