IFN-g 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

Previous studies indicated that the Tat protein of HIV functions as a progression factor in Kaposi’s sarcoma (KS), an angiopro-liferative disease common and aggressive in HIV-1-infected individuals (AIDS-KS). In particular, Tat that is released by infected cells stimulates the growth and invasion of spindle cells of endothelial origin derived from KS lesions (KS cells). Other work suggested that inflammatory cytokines may act as initiating factors in KS since they induce normal endothelial cells to acquire the same phenotype and functional features of KS cells, including the responsiveness to Tat. In this study, we show that among the inflammatory cytokines increased in AIDS-KS lesions, IFN-g alone is sufficient to induce endothelial cells to proliferate and to invade the extracellular matrix in response to Tat. This is because IFN-g up-regulates the expression and activity of the receptors for Tat identified as the integrins a5b1 and avb3. These results suggest that, by triggering Tat effects, IFN-g plays a major role in AIDS-KS pathogenesis. The Journal of Immunology, 1999, 162: 1165–1170. K aposi’s sarcoma (KS)3 is a proliferative disease of vas-cular origin that is more frequent and aggressive in HIV-1-infected homosexual men (AIDS-KS) as compared with classical KS, which is rare and indolent (1–3). In early stages, KS is characterized by endothelial cell activation and proliferation, angiogenesis, and inflammatory cell infiltration (4–9). This is fol-lowed by the appearance of the typical spindle-shaped cells (KS cells) that represent a heterogeneous population dominated by ac