Interleukin-1 beta increases the BCL-2/BAX ratio in Kaposi's sarcoma cells.
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.
Simonart
Thierry
T
Department of Dermatology, Erasme University Hospital, B-1070 Brussels, Belgium. tsimonar@ulb.ac.be
Van Vooren
Jean-Paul
JP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D003114:Colony-Forming Units Assay / Q000379:methods; D016895:Culture Media, Serum-Free / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000637:transplantation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D016895:Culture Media, Serum-Free; D007375:Interleukin-1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein