Interleukin 13 inhibits growth of human renal cell carcinoma cells independently of the p140 interleukin 4 receptor chain.
Interleukin-13 (IL-13) is a cytokine produced primarily by activated T lymphocytes. It exerts a variety of effects on different cell types, including monocytes, B lymphocytes, mast cells, and keratinocytes. The effects of IL-13 on target cells are often similar to the effects of IL-4, which is another cytokine product of activated T lymphocytes. We recently described the expression of intermediate- to high-affinity receptors for IL-13 (IL-13R) on renal cell carcinoma (RCC) cells. In the present study, we examined the effect of IL-13 on the growth of RCC cells as measured by [3H]thymidine uptake and a clonogenic assay. In addition, we used an IL-4R-specific antibody to examine the specificity of IL-4R and IL-13R binding and function. We observed that IL-13 inhibited RCC cell proliferation by up to 50% and colony formation by up to 32% when compared with cells cultured in medium alone. A combination of IL-4 and IL-13 did not have an additive or synergistic effect on the growth of RCC cells. These cells expressed mRNA for IL-13 and secreted immunoreactive IL-13 protein in culture. The growth-inhibitory effects of IL-13 were specific, because they were not affected by antibodies to IL-4 or to the 140-kilodalton subunit of IL-4R. Furthermore, polyclonal antibodies to IL-4R failed to inhibit the binding of 125I-IL-13 to RCC cells. These results indicate that IL-13 has significant antiproliferative effects on human RCC cells, and the inhibition of IL-13 effects by anti-IL-4R antibody previously reported in lymphoid cells does not occur in RCC cells.
Obiri
N I
NI
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. OBIRI@A1.CBER.FDA.GOV
Husain
S R
SR
Debinski
W
W
Puri
R K
RK
D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D019948:Receptors, Interleukin-4 / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D018793:Interleukin-13; D019948:Receptors, Interleukin-4