COMBINATIONS OF INTERFERON-GAMMA AND RETINOIC ACID OR "1-ALPHA,25-DIHYDROXYCHOLECALCIFEROL INDUCE DIFFERENTIATION OF THE HUMAN MONOBLAST LEUKEMIA-CELL LINE U-937

  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (7) , 675-679
Abstract
The monoblastlike leukemia cell line, U-937, is induced to differentiate into monocytelike cells by incubation with 200-500 U/ml of recombinant human immune interferon (IFN-.gamma.) judging from capacity to reduce nitroblue tetrazolium. At least an additive differentiation-inducing effect was found between IFN-.gamma. and 1-100 nM retinoic acid (RA). A marked synergistic differentiation-inducing effect was found between IFN-.gamma. and 0.1-1.0 nM 1.alpha.,25-dihydroxycholecalciferol (1,25[OH]2D3). It is also shown that U-937 can be primed for differentiation by treatment for approximately one day with 1,25(OH)2D3 followed by exposure to IFN-.gamma.. Priming of these cells does not depend on the normal rate of RNA synthesis, as it occurs even better in the presence of cordycepin, suggesting that a decrease in RNA synthesis favors IFN-induced differentiation. Actually, the addition of cordycepin during initial incubation with IFN increased the subsequent response to IFN-.gamma. (and also to RA and 1,25[OH]2D3). These results, indicating that combinations of IFN-.gamma. and either RA or 1,25(OH)2D3 induce differentiation of U-937, may be of importance in combination biotherapy of leukemia.

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