AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6.
Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1 beta, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, we examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. We found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [3H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at greater than 10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. The decrease from IL-6 antisense in AIDS-KS cell proliferation was reversed by the addition of hrIL-6. We confirmed that AIDS-KS cells produced IL-6 in vivo by preparing RNA and tissue sections from involved and uninvolved skin from a patient with AIDS Kaposi sarcoma. We detected immunoreactive IL-6 in the involved tumor areas and to a lesser extent in the surrounding normal epidermis. Slot blot hybridization showed a great excess of IL-6 and IL-6-R RNA in involved skin compared to uninvolved skin. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells.
Miles
S A
SA
Division of Hematology-Oncology, University of California School of Medicine, Los Angeles 90024.
Rezai
A R
AR
Salazar-González
J F
JF
Vander Meyden
M
M
Stevens
R H
RH
Logan
D M
DM
Mitsuyasu
R T
RT
Taga
T
T
Hirano
T
T
Kishimoto
T
T
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology*; D015152:Blotting, Northern; D015870:Gene Expression; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012313:RNA; D016372:RNA, Antisense; D011971:Receptors, Immunologic / Q000502:physiology; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D015850:Interleukin-6; D016372:RNA, Antisense; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D012313:RNA