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Journal of Virology, November 2002, p. 11570-11583, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11570-11583.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Interleukin-8 and Growth-Regulated Oncogene Alpha Mediate Angiogenesis in Kaposi's Sarcoma

Brian R. Lane,1,2 Jianguo Liu,3 Paul J. Bock,1 Dominique Schols,4 Michael J. Coffey,5 Robert M. Strieter,5,{dagger} Peter J. Polverini,3,{ddagger} and David M. Markovitz1,2*

Divisions of Infectious Diseases,1 Pulmonary and Critical Care Medicine, Department of Internal Medicine,5 Graduate Program in Cellular and Molecular Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0640,2 Department of Oral Medicine, Pathology, and Oncology, University of Michigan Dental School, Ann Arbor, Michigan 48109,3 Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium4

Received 13 March 2002/ Accepted 13 August 2002

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}.

* Corresponding author. Mailing address: 5220 MSRB III, 1150 West Medical Center Dr., Ann Arbor, MI 48109-0640. Phone: (734) 647-1786. Fax: (734) 764-0101. E-mail: dmarkov{at}umich.edu.

{dagger} Present address: Division of Pulmonary and Critical Care Medicine, Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1922.

{ddagger} Present address: University of Minnesota School of Dentistry, Minneapolis, MN 55455.

Journal of Virology, November 2002, p. 11570-11583, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11570-11583.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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