Up-regulation of intercellular adhesion molecule 1 (ICAM-1) on human renal cell carcinoma cells by interleukin-4.
We have previously demonstrated that human renal cell carcinoma (RCC) cells express high-affinity IL-4 receptors (IL-4R). To study the functions of these receptors, we have examined the effect of IL-4 on the expression of intercellular adhesion molecule-1 (ICAM-1 or CD54) on human RCC cells. Following incubation with various concentrations of IL-4, RCC cells were examined for ICAM-1 expression by flow cytometric analysis. The 2 primary RCC cell cultures and the 2 cell lines examined expressed varying basal levels of ICAM-1 on the cell surface. IL-4 treatment increased ICAM-1 expression in a time-dependent manner and maximum augmentation of ICAM-1 expression was observed after a 48 hr incubation. The increase in ICAM-1 expression was specific because anti-hIL-4 antibody blocked this effect. No enhancement of ICAM-1 expression was observed when RCC cells were incubated with IL-4 in the presence of cycloheximide, indicating that the IL-4 effect requires new protein synthesis. Up-regulation of ICAM-1 expression was also observed at the mRNA level and maximum increase in message occurred 8 hr post-IL-4 treatment. Both IL-4 and IFN-gamma also increased soluble ICAM-1 levels in WS-RCC culture supernatant. The significance of enhanced soluble and surface ICAM-1 expression was investigated by examining the lymphokine activated killer (LAK) cell-mediated lysis of IL-4-treated WS-RCC cells. LAK cells lysed WS-RCC cells very effectively, but lysis observed in target cells pre-treated with IL-4 did not correlate with the increased expression of ICAM-1 antigen. Our results indicate a previously unknown function of IL-4 on RCC and further demonstrate that IL-4R on RCC are functional.
Obiri
N I
NI
Laboratory of Molecular Tumor Biology, FDA, Bethesda, MD 20892-4555, USA.
Tandon
N
N
Puri
R K
RK
D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell; D003513:Cycloheximide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007680:Kidney Neoplasms; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma; D003513:Cycloheximide