Human keratinocyte sensitivity towards inflammatory cytokines varies with culture time.
Proliferating keratinocyte cultures have been reported to synthesize higher concentrations of prostaglandin (PG) E than confluent ones. As interleukin-1 (IL-1) stimulates keratinocyte PGE synthesis we investigated whether the degree of confluency of the keratinocyte culture modified the response of the cells to IL-1. It was found that IL-1alpha (100 U/ml) stimulated PGE(2) synthesis by proliferating (7 days in culture) but not differentiating (14 days in culture) keratinocytes. Similar effects were observed using tumour necrosis factor-alpha. Both arachidonic acid (AA) and the calcium ionophore A23187 stimulated PGE(2) synthesis by 7 and 14 day cultures although the increase was greatest when 7 day cultures were used. Our data indicate that there is a specific down-regulation of the mechanism(s) by which some inflammatory cytokines stimulate keratinocyte eicosanoid synthesis as cultured keratinocytes begin to differentiate.
Elliott
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Department of Pharmacology Medical Biological Laboratory T.N.O. P.O. Box 45 Rijswijk 2280 AA The Netherlands.
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