Damage to the skin induced by chemical irritants is associated with the release of arachidonic acid metabolites, such as prostaglandin E(2) (PGE(2)) which plays an important role in epidermal inflammation. This study investigated cytotoxicity and release of PGE(2) in human epidermal keratinocytes following an 18 hr exposure of confluent cultures to various skin irritants. The concentration-dependent release of PGE, into the extracellular medium appeared to fall into two categories, which was reflective of possible mechanisms of action. Potent skin irritants, such as phorbol-12-myristate-13-acetate, benzalkonium chloride and tributyltin chloride, elicited an increase in extracellular PGE(2) levels at concentrations that did not produce overt cell damage (uptake of neutral red at these concentrations was comparable to control levels). Non-irritants (2-methoxyethanol and 2-butoxyethyl acetate) and two less severe irritants (sodium dodecyl sulfate and acetic acid) stimulated release of PGE(2) only at concentrations that compromised cellular integrity (uptake of neutral red was at least 50% lower than that of control cultures).
