Relationship between the proliferation of keratinocytes cultured in vitro and prostaglandin E(2)

In the growth of keratinocytes ''in vitro'', PGE(2) seems to play an important role. We have shown that in fibroblast-keratinocyte co-cultures, indomethacin, employed at concentrations which inhibit the PGE(2) synthesis, reduced the proliferation of epidermal cells. This effect was reversed by an exogenous PGE(2) addition to the culture media. To better understand the relationship between keratinocytes and the autacoid, we have tested PGE(2) at various concentrations in different cultural conditions, that is, epidermal cells were grown on a 3T3-J(2) feeder layer, without fibroblasts and with a 3T3-J(2) 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. PGE(2) induced significant morphological and morphometrical variations only if added to the contitioning 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 PGE(2) inhibits cell differentiation. Thus PGE(2) action on keratinocytes seems to be strictly related to the presence of dermal cells.