IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4).
Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a single 4 kB IL-4R-specific mRNA and 1828 +/- 408 high affinity IL-4 binding sites per cell with a dissociation constant (Kd) of 154 +/- 37 pM. Addition of recombinant human IL-4 (rIL-4) minimally inhibited AIDS-KS cell growth and expression of IL-6. We then studied the effects of a chimeric fusion toxin DAB389-IL-4 which exerts cellular toxicity only on cells expressing IL-4R. DAB389-IL-4 inhibited protein synthesis in AIDS-KS cells at low concentrations (IC50 of 5 x 10(-11) M). This effect was abrogated by neutralizing antibody to IL-4 (25D2). We conclude that KS cells express a functional IL-4R and this receptor could serve as a target for novel therapy with agents such as DAB389-IL-4.
Cai
J
J
Department of Medicine, University of Southern California, Los Angeles, USA.
Zheng
T
T
Murphy
J
J
Waters
C A
CA
Lin
G Y
GY
Gill
P S
PS
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007457:Iodine Radioisotopes; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000378:metabolism*
D000970:Antineoplastic Agents; C093203:DAB(389)-interleukin 4; D004167:Diphtheria Toxin; D000922:Immunotoxins; D015850:Interleukin-6; D007457:Iodine Radioisotopes; C508351:OSM protein, human; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D053683:Oncostatin M; D015847:Interleukin-4