The role of human immunodeficiency virus-I in the pathogenesis of acquired immunodeficiency syndrome-related Kaposi's sarcoma: the importance of an inflammatory and angiogenic milieu.
People infected with human immunodeficiency virus type-I (HIV-I) have an increased incidence of Kaposi's sarcoma (KS) and HIV-I infection alters the natural history of KS. The potent trans-activator HIV-I protein Tat plays a major role in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS. Among many of its KS-promoting activities, the Tat protein augments the angiogenic activities of basic fibroblast growth factor (bFGF), interferon gamma, and vascular endothelial growth factor (VEGF); it also mimics the effects of the extramedullary matrix proteins fibronectin and vitronectin, and increases the expression of matrix metalloproteinases. Inflammatory cytokines induce endothelial cells to acquire the phenotype and functional features of AIDS-related KS spindle cells. These cytokines act by both autocrine and paracrine mechanisms. The synergy between cytokines and the HIV-I Tat protein provides possible insight into why AIDS-related KS is more aggressive than the classic Mediterranean form, in which the HIV-I Tat protein does not play a role.
Dezube
B J
BJ
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000821:virology; D016207:Cytokines / Q000502:physiology; D015696:Gene Products, tat / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000502:physiology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation; D018919:Neovascularization, Physiologic; D012514:Sarcoma, Kaposi / Q000209:etiology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D015696:Gene Products, tat; D012739:Gonadal Steroid Hormones; D054322:tat Gene Products, Human Immunodeficiency Virus