IFN-gamma induces endothelial cells to proliferate and to invade the extracellular matrix in response to the HIV-1 tat protein: Implications for AIDS-Kaposi's sarcoma pathogenesis

Previous studies indicated that the Tat protein of HIV functions as a progr ession factor in Kaposi's sarcoma (KS), an angioproliferative disease commo n and aggressive in HIV-l-infected individuals (AIDS-KS), In particular, Ta t that is released by infected cells stimulates the growth and invasion of spindle cells of endothelial origin derived from KS lesions (KS cells). Oth er work suggested that inflammatory cytokines may act as initiating factors in KS since they induce normal endothelial cells to acquire the same pheno type and functional features of KS cells, including the responsiveness to T at, In this study, we show that among the inflammatory cytokines increased in AIDS-KS lesions, IFN-gamma alone is sufficient to induce endothelial cel ls to proliferate and to invade the extracellular matrix in response to Tat , This is because IFN-gamma up-regulates the expression and activity of the receptors for Tat identified as the integrins alpha(5)beta(1) and alpha(v) beta(3). These results suggest that, by triggering Tat effects, IFN-gamma p lays a major role in AIDS-KS pathogenesis.