Interleukin-1 beta increases the BCL-2/BAX ratio in Kaposi's sarcoma cells

Cytokine. 2002 Sep 21;19(6):259-66. doi: 10.1006/cyto.2002.1964.

Abstract

Interleukin-1 (IL-1) is a multifunctional cytokine known to act as a growth factor for AIDS-KS cells. In addition to its mitogenic effects, we found that IL-1 induced the protection of KS cells from apoptotic death induced by serum deprivation in a dose-dependent manner. AIDS-KS cells as well as cells derived from iatrogenic and sporadic KS exhibited a similar response to IL-1, which stresses the key role of this cytokine in the pathogenesis of KS regardless of its epidemiological form. Using both an immunohistochemical and an immunoblot approach, we found that IL-1 increased the expression of Bcl-2 and decreased that of Bax, while having no effect on the expression of Bclx(L), Fas and CD40. The effects of IL-1 were inhibited by IL-1ra, suggesting that imbalance between these two counter-acting cytokines may contribute to the altered accumulation of KS spindle cells. Our findings may provide a link between KS cell escape from apoptosis and the immune dysregulation known to be associated with KS.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Count
  • Cell Division / physiology
  • Colony-Forming Units Assay / methods
  • Culture Media, Serum-Free / metabolism
  • Culture Media, Serum-Free / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-1 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplastic Stem Cells / transplantation
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / pathology*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Bax protein, mouse
  • Culture Media, Serum-Free
  • Interleukin-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein