Interleukin-8 and growth-regulated oncogene alpha mediate angiogenesis in Kaposi's sarcoma.
The development of the complex neoplasm Kaposi's sarcoma is dependent on infection with the Kaposi's sarcoma-associated herpesvirus (KSHV) and appears to be greatly enhanced by cytokines and human immunodeficiency virus type 1 (HIV-1) Tat. Interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-alpha) are chemokines involved in chemoattraction, neovascularization, and stimulation of HIV-1 replication. We have previously demonstrated that production of GRO-alpha is stimulated by exposure of monocyte-derived macrophages (MDM) to HIV-1. Here we show that exposure of MDM to HIV-1, viral Tat, or viral gp120 leads to a substantial increase in IL-8 production. We also demonstrate that IL-8 and GRO-alpha are induced by KSHV infection of endothelial cells and are crucial to the angiogenic phenotype developed by KSHV-infected endothelial cells in cell culture and upon implantation into SCID mice. Thus, the three known etiological factors in Kaposi's sarcoma pathogenesis-KSHV, HIV-1 Tat, and cellular growth factors-might be linked, in part, through induction of IL-8 and GRO-alpha.
Lane
Brian R
BR
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0640, USA.
Liu
Jianguo
J
Bock
Paul J
PJ
Schols
Dominique
D
Coffey
Michael J
MJ
Strieter
Robert M
RM
Polverini
Peter J
PJ
Markovitz
David M
DM
D000818:Animals; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods; D054360:Chemokine CXCL1; D018925:Chemokines / Q000378:metabolism / Q000494:pharmacology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D015696:Gene Products, tat / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000276:immunology; D009389:Neovascularization, Pathologic; D012514:Sarcoma, Kaposi / Q000098:blood supply* / Q000473:pathology*; D054322:tat Gene Products, Human Immunodeficiency Virus
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D054322:tat Gene Products, Human Immunodeficiency Virus