H. Schwende et al., DIFFERENCES IN THE STATE OF DIFFERENTIATION OF THP-1 CELLS INDUCED BYPHORBOL ESTER AND 1,25-DIHYDROXYVITAMIN D-3, Journal of leukocyte biology, 59(4), 1996, pp. 555-561
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.