Cytotoxic effect of TNF-alpha and abnormal regulation of cAMP in the retinoid resistant cell line U937/GTB.

: We have studied the effect of retinoids, forskolin and TNF-alpha on two sublines of U937 cells, U937/clone 4 and U937/GTB. Retinoids induced differentiation of U937/clone 4, while the U937/GTB cells were resistant to induction of differentiation by retinoids. Retinoids effectively reduced the proliferation of both U937/clone 4 and U937/GTB, and decreased the steady state levels of c-myc mRNA in both sublines. Furthermore, the retinoid resistant U937/GTB cells were hypersensitive to the cytotoxic effect of TNF-alpha. Forskolin increased the cAMP level in the U937/clone 4 cells 14 times above basal level, but did not change the cAMP concentration in the U937/GTB cells.