Effects of interleukin-1 and interleukin-1 receptor antagonist in AIDS-Kaposi's sarcoma.
Kaposi's sarcoma (KS) is the most common tumor seen in patients with HIV-1 infection. HIV-1 may induce KS directly through viral protein(s) or indirectly through regulation of cytokines such as IL-1 and IL-6. We have shown that AIDS-KS spindle cells express IL-1 beta and that IL-1ra inhibits KS-spindle cell growth. IL-1ra had little effect on human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASM), and human foreskin fibroblast (NN41). These findings support an autocrine activity for IL-1. Furthermore, exogenous IL-1 can enhance AIDS-KS cell growth, and this effect is completely blocked by IL-1ra. As expected, IL-1ra also blocks IL-1 mediated upregulation of IL-6 and bFGF, both of which are autocrine growth factors for KS. IL-1ra is thus a potential candidate for the treatment of AIDS-associated KS.
Louie
S
S
Kenneth Norris Jr. Cancer Center, University of Southern California, Los Angeles 90033, USA.
Cai
J
J
Law
R
R
Lin
G
G
Lunardi-Iskandar
Y
Y
Jung
B
B
Masood
R
R
Gill
P
P
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000096:biosynthesis; D015497:HIV-1; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D053683:Oncostatin M; D010452:Peptide Biosynthesis; D010455:Peptides; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M; D013936:Thymidine