Transforming growth factor-beta potentiates vitamin D3-induced terminal monocytic differentiation of human leukemic cell lines.

摘要: We have investigated the effects of 1,25-dihydroxyvitamin D3 (D3) and/or transforming growth factor (TGF)-beta on one monocytic (U-937) and two human promyelocytic (HL-60 AML-193) leukemic cell lines. addition induces a partial maturation lines, whereas TGF-beta treatment is largely ineffective. Combined with causes terminal maturation, as evaluated both by assessment large spectrum membrane Ag functional assays. Furthermore, sequential inducers showed that pretreatment 1 followed incubation D3, but not vice versa, effectively simultaneous agents. In liquid culture proliferative activity these lines slightly decreased virtually unaffected TGF-beta, combined markedly potentiated inhibitory effect. TGF-beta/D3 (but alone) elicits expression CD14, FcRI, FcRII, CD11a, CD11b, CD11c, ICAM-1, PECAM-1 at level comparable to observed normal monocytes. It noteworthy several play an important role in monocyte physiology (e.g., CD14 mediates binding bacterial LPS monocytes). Treatment superoxide anions H2O2 production similar circulating semisolid culture, alone cause, respectively, marked slight loss cloning efficiency their synergistically results complete capacity. These findings suggest physiologic for maturation. they may pave way design clinical protocols combining differentiation therapy acute promyelocytic/myelomonocytic leukemia.