PGE(2) is produced by cells of the thymic microenvironment. The effect
s of PGE(2) are mediated by cAMP through binding to its intracellular
receptor protein kinase A (PKA). Phorbol 12-myristate 13-acetate (PMA)
is known to modulate CD molecule expression on thymocytes, probably t
hrough activation of protein kinase C (PKC). We have hypothesized that
cross-talk between these two signalling pathways may affect modulatio
n of the CD molecules on the cell surface of thymocytes. For this purp
ose, we compare the effects of PMA alone or combined with PGE(2) on CD
3, CD4 and CD8 expression on mouse thymocytes by flow-cytometric analy
sis. PMA treatment almost completely abolished CD4 expression and slig
htly decreased CD3 and CD8 expression. PGE(2) alone did not change the
CD3, CD4 and CD8 molecule expression. Combined with PMA, PGE(2) can o
vercome the decrease induced by PMA of the CD3 expression and partiall
y reduced the disappearance of the CD4 molecule. On the other hand PGE
(2) accelerated the loss of CD8 molecule expression. These events occu
rred only in CD4+ CD8+ immature thymocytes. An analogue of cAMP (dibut
ryl cAMP) mimics the effect of PGE(2), but not Br-cGMP. This different
ial regulation by PGE(2) of the CD molecule expression on immature thy
mocytes may provide additional evidence on the role of PGE(2) during t
he process of thymic differentiation. (C) 1998 Elsevier Science B.V. A
ll rights reserved.