Relationship between the proliferation of keratinocytes cultured in vitro and prostaglandin E2

In the growth of keratinocytes "in vitro", PGE2 seems to play an important role. We have shown that in fibroblast-keratinocyte co-cultures, indomethacin, employed at concentrations which inhibit the PGE2 synthesis, reduced the proliferation of epidermal cells. This effect was reversed by an exogenous PGE2 addition to the culture media. To better understand the relationship between keratinocytes and the autacoid, we have tested PGE2 at various concentrations in different cultural conditions, that is, epidermal cells were grown on a 3T3-J2 feeder layer, without fibroblasts and with a 3T3-J2 conditioned medium. We observed an increase in keratinocyte proliferation induced by the autacoid alone in the presence of fibroblasts, while a severe inhibitory effect was relieved when dermal cells or the conditioning medium were absent. The lack of fibroblasts and their products in the culture medium modified the morphology of keratinocytes cultured in vitro. PGE2 induced significant morphological and morphometrical variations only if added to the conditioning medium. The autacoid decreased the expression of 66 kDa protein, if cells were grown in the presence of fibroblasts or with conditioning medium, whereas it completely inhibited this keratin and those of 60, 54 kDa if cells were cultured only with a basal medium. From morphometrical and electrophoretical data we can suppose that PGE2 inhibits cell differentiation. Thus PGE2 action on keratinocytes seems to be strictly related to the presence of dermal cells.