Vimentin expression as a late event in the in vitro differentiation of human promonocytic cells.

The administration of either 12-O-tetradecanoyl phorbol-13-acetate (TPA, 3 x 10(-8) M), sodium butyrate (SB, 10(-3) M), N6,2'-O-dibutyryladenosine-3':5'-cyclic monophosphate (dbcAMP, 10(-3) M), cytosine arabinoside (ara-C, 10(-7) M), amsacrine (mAMSA, 10(-7) M) or retinoic acid (RA, 10(-6) M) inhibits the growth activity of human promonocytic U-937 cells, by arresting them at G1 or at the G1/S border (SB, RA, ara-C), at G2 (mAMSA) or at G1 and G2 (dbcAMP). All these agents trigger cell differentiation, as proved by the increased expression of the maturation-associated CD11b and CD11c surface antigens, and induce the expression of the vimentin gene at both the protein and the mRNA levels. TPA, SB and dbcAMP behave as "early" inducers, in the sense that vimentin mRNA levels are rapidly increased (hour 6) upon drug administration. In contrast, mAMSA and RA behave as "late" inducers, since they do not increase vimentin mRNA levels until 48 to 72 hours, following the stimulation of surface antigen expression. The action of RA is characterized by an initial inhibition period, in which the basal level of vimentin mRNA is abolished (hour 24). Nevertheless, this RNA is later re-induced, to reach at 72 hours higher levels than in untreated cells. Moreover, RA is capable of delaying the early induction of vimentin expression caused by TPA and SB, without affecting the normal expression of differentiation markers. Taken together, these results strongly suggest that vimentin expression is not required at the initial stages of promonocytic cell differentiation, although it could play a role at an advanced stage.