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

AIDS-related Kaposi sarcoma (AIDS-KS) is the most common malignancy as sociated with HIV infection, with an incidence of 10-30% of all AIDS p atients. As such, there have been a large number of AIDS-KS cell strai ns isolated and numerous studies conducted to elucidate the mechanisms of malignancy in this disease. We have reported histological grade as sociated differences in the ability of AIDS-KS cell strains to prolife rate under conditions of minimal growth factor supplementation, with s trains derived from high grade lesions having enhanced proliferation p otential. Furthermore, we found that this difference in in vitro growt h characteristics was not attributed to grade associated differences i n autologous growth factor release. These current investigations explo red the hypothesis that grade associated growth differences could be a ttributed to differences in the expression of the components of the IL -6 receptor, or expression/inducibility of the pleotrophic transcripti on factor NF-kappa B. We determined there were no significant grade as sociated differences in the expression of either component (IL-6R alph a chain or gp130) of the IL-6 receptor. However, non-lesional oral der ived cell strain lysates from AIDS-KS patients (n=4) contained signifi cantly lower concentrations of both components of the IL-6 receptor th an AIDS-KS strains (n=8) and lower concentrations of gp-130 than norma l human oral derived fibroblasts (n=2). Comparative analysis of sera c oncentrations of soluble components of the IL-6 receptor did not demon strate significant differences between HIV+/KS+(n=7), HIV+/KS-(n=9) an d normal (HIV-/KS-) (n=4) populations. Further, no differences were de tected in the expression of NF-kappa B in AIDS-KS cell strains (n=5) d erived from both high and low histological grade lesions as compared t o nonlesional AIDS-KS cell stain (n=1) and normal human oral derived f ibroblasts (n=2) under conditions of: constitutive/proliferative growt h, sera starvation, oxidative stress, and mitogen reintroduction after sera starvation. In conclusion, these investigations have eliminated two explanations for histological grade associated differences for in vitro growth potential of AIDS-related KS cell strains and further sub stantiated the lack of systemic paracrine cytokine/cytokine receptor e ffects in AIDS-KS pathogenesis.