Abstract
Kaposi's sarcoma (KS) is the most common tumor associated with HIV-1 infection. Here, we report the expression, regulation, and biological effect of interleukin (IL)-8 in KS. AIDS-KS cell lines expressed higher levels of IL-8 than either human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle (AoSM) cells or fibroblast cells (T1). The inflammatory cytokine IL-1beta up-regulated IL-8 expression in a time- and concentration-dependent manner in KS cell lines. IL-8 antisense oligonucleotides specifically reduced IL-8 mRNA and protein levels and inhibited KS cell growth in a dose-dependent manner. In addition, supernatant from a KS cell line induced the growth of HUVECs and angiogenesis in chicken chorioallantoic membrane assays, both of which were inhibited by IL-8 neutralizing antibody. Serum levels of IL-8 were also elevated in KS cases compared with matched controls. Modulation of IL-8 may thus be of therapeutic value in this disease.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Biomarkers, Tumor / analysis
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Cell Division / drug effects
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Cell Line
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Culture Media, Conditioned / pharmacology
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DNA, Antisense / pharmacology
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Neoplastic / drug effects
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Growth Substances / genetics*
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Growth Substances / metabolism
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Humans
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Immunohistochemistry
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Interleukin-1 / pharmacology
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Interleukin-8 / genetics*
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Interleukin-8 / immunology
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Interleukin-8 / pharmacology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neovascularization, Physiologic / drug effects
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Oligonucleotides / pharmacology
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / drug effects
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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Receptors, Interleukin-8A / analysis
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Receptors, Interleukin-8A / genetics
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Sarcoma, Kaposi / genetics*
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Sarcoma, Kaposi / metabolism
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Sarcoma, Kaposi / prevention & control
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Tumor Cells, Cultured
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Up-Regulation / drug effects
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Biomarkers, Tumor
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Culture Media, Conditioned
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DNA, Antisense
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Growth Substances
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Interleukin-1
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Interleukin-8
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Oligonucleotides
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Interleukin-8A
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Recombinant Proteins