DIFFERENCES IN THE STATE OF DIFFERENTIATION OF THP-1 CELLS INDUCED BYPHORBOL ESTER AND 1,25-DIHYDROXYVITAMIN D-3

Human THP-1 leukemia cells differentiate along the monocytic lineage f ollowing exposure to phorbol-12-myristate-13-acetate (PMA) or 1,25-dih ydroxyvitamin D-3 (VD3). In the monocytic cell line THP-1, PMA treatme nt resulted in a more differentiated phenotype than VD3, according to adherence, loss of proliferation, phagocytosis of latex beads, and exp ression of CD11b and CD14. Both differentiating substances induced sim ilar effects in the release of superoxide anions (O-2 .) VD3-different iated cells did not release prostaglandin E(2) (PGE(2)), in contrast t o PMA-differentiated cells, and in PMA-differentiated cells phospholip ase A(2) (PLA(2)) activity and expression was increased. Lipopolysacch aride (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) release was higher in PMA-treated cells, PMA- but not VD3-differentiation res ulted in a translocation of protein kinase C (PKC) isoenzymes to membr ane fractions. Both differentiating agents up-regulated the expression of PKC isoenzymes. Whereas VD3 elevated mainly the expression of PKC- beta, PMA caused a strong increase in PKC-delta and a weak increase in PKC-alpha, PKC-epsilon, and PKC-zeta expression. These results indica te that phorbol ester and the active metabolite of vitamin D induce di fferent signal pathways, which might result in different achievement o f differentiation.