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

J Immunol. 1999 Jan 15;162(2):1165-70.

Abstract

Previous studies indicated that the Tat protein of HIV functions as a progression factor in Kaposi's sarcoma (KS), an angioproliferative 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-gamma alone is sufficient to induce endothelial cells 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 alpha5beta1 and alpha(v)beta3. These results suggest that, by triggering Tat effects, IFN-gamma plays a major role in AIDS-KS pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / pathology*
  • Acquired Immunodeficiency Syndrome / virology
  • Cell Division / immunology
  • Cell Movement / immunology*
  • Cells, Cultured
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / virology
  • Extracellular Matrix / pathology*
  • Extracellular Matrix / virology
  • Gene Products, tat / metabolism
  • Gene Products, tat / physiology*
  • Growth Substances / physiology
  • HIV-1 / physiology
  • Humans
  • Interferon-gamma / physiology*
  • Receptors, Fibronectin / biosynthesis
  • Receptors, Fibronectin / physiology
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / physiology
  • Receptors, Vitronectin / biosynthesis
  • Receptors, Vitronectin / physiology
  • Sarcoma, Kaposi / etiology*
  • Sarcoma, Kaposi / pathology
  • Sarcoma, Kaposi / virology
  • Umbilical Veins
  • Up-Regulation / immunology
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, tat
  • Growth Substances
  • Receptors, Fibronectin
  • Receptors, Virus
  • Receptors, Vitronectin
  • tat Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma