IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4).

Abstract

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.

• Authors: J Cai, T Zheng, J Murphy, C A Waters, G Y Lin, P S Gill
• Journal: Investigational new drugs (Invest New Drugs) Vol. 15 Issue 4 Pg. 279-87 ( 1997) ISSN: 0167-6997 [Print] United States
• PMID: 9547670 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• DAB(389)-interleukin 4
• Diphtheria Toxin
• Immunotoxins
• Interleukin-6
• Iodine Radioisotopes
• OSM protein, human
• Peptides
• Protein Synthesis Inhibitors
• Receptors, Interleukin-4
• Recombinant Fusion Proteins
• Oncostatin M
• Interleukin-4

Topics

• Acquired Immunodeficiency Syndrome (metabolism)
• Antineoplastic Agents (pharmacology)
• Blotting, Northern
• Cell Division (drug effects)
• Cells, Cultured
• Diphtheria Toxin (pharmacology)
• Humans
• Immunotoxins (pharmacology)
• Interleukin-4 (pharmacology)
• Interleukin-6 (biosynthesis)
• Iodine Radioisotopes
• Oncostatin M
• Peptides (pharmacology)
• Protein Synthesis Inhibitors (pharmacology)
• Receptors, Interleukin-4 (biosynthesis)
• Recombinant Fusion Proteins (pharmacology)
• Sarcoma, Kaposi (metabolism)