Ni. Obiri et al., UP-REGULATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) ON HUMAN RENAL-CELL CARCINOMA-CELLS BY INTERLEUKIN-4, International journal of cancer, 61(5), 1995, pp. 635-642
We have previously demonstrated that human renal cell carcinoma (RCC)
cells express high-affinity IL-4 receptors (IL-4R). To study the funct
ions of these receptors, we have examined the effect of IL-4 on the ex
pression of intracellular adhesion molecule-I (ICAM-I or CD54) on huma
n RCC cells. Following incubation with various concentrations of IL-4,
RCC cells were examined for ICAM-I expression by flow cytometric anal
ysis. The 2 primary RCC cell cultures and the 2 cell lines examined ex
pressed varying basal levels of ICAM-I on the cell surface. IL-4 treat
ment increased ICAM-I expression in a time-dependent manner and maximu
m augmentation of ICAM-I expression was observed after a 48 hr incubat
ion. The increase in ICAM-I expression was specific because anti-hIL-4
antibody blocked this effect. No enhancement of ICAM-I expression was
observed when RCC cells were incubated with IL-4 in the presence of c
ycloheximide, indicating that the IL-4 effect requires new protein syn
thesis. Up-regulation of ICAM-I expression was also observed at the mR
NA level and maximum increase in message occurred 8 hr post-IL-4 treat
ment. Both IL-4 and IFN-gamma also increased soluble ICAM-I levels in
WS-RCC culture supernatant. The significance of enhanced soluble and s
urface ICAM-I expression was investigated by examining the lymphokine
activated killer (LAK) cell-mediated lysis of IL-4-treated WS-RCC cell
s. LAK cells lysed WS-RCC cells very effectively, but lysis observed i
n target cells pre-treated with IL-4 did not correlate with the increa
sed expression of ICAM-I antigen. Our results indicate a previously un
known function of IL-4 on RCC and further demonstrate that IL-4R on RC
C are functional. (C) 1995 Wiley-Liss, Inc.