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....

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Bibliographic Details
Published in:Investigational new drugs 1997, Vol.15 (4), p.279-287
Main Authors: Cai, J, Zheng, T, Murphy, J, Waters, C A, Lin, G Y, Gill, P S
Format: Article
Language:English
Subjects:
Acquired Immunodeficiency Syndrome - metabolism
Antibodies
Antineoplastic Agents - pharmacology
Binding sites
Blotting, Northern
Cell Division - drug effects
Cell growth
Cells, Cultured
Chromatography
Cytokines
Cytotoxicity
Diphtheria
Diphtheria Toxin - pharmacology
Humans
Immunotoxins - pharmacology
Interleukin-4 - pharmacology
Interleukin-6 - biosynthesis
Iodine Radioisotopes
Kaposis sarcoma
Laboratories
Oncostatin M
Penicillin
Peptides - pharmacology
Protein synthesis
Protein Synthesis Inhibitors - pharmacology
Proteins
Receptors, Interleukin-4 - biosynthesis
Recombinant Fusion Proteins - pharmacology
Ribonucleic acid
RNA
Sarcoma, Kaposi - metabolism
Toxicity
Toxins
Tumor necrosis factor-TNF
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Summary: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.
ISSN:0167-6997
1573-0646
DOI:10.1023/A:1005958123893