Interleukin 8 is an autocrine growth factor and a surrogate marker for Kaposi's sarcoma.
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.
Masood
R
R
University of Southern California Keck School of Medicine, Los Angeles, California 90089-9172, USA. masood@hsc.usc.edu
Cai
J
J
Tulpule
A
A
Zheng
T
T
Hamilton
A
A
Sharma
S
S
Espina
B M
BM
Smith
D L
DL
Gill
P S
PS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009841:Oligonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D016373:DNA, Antisense; D006133:Growth Substances; D007375:Interleukin-1; D016209:Interleukin-8; D009841:Oligonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins