DIFFERENTIAL-EFFECTS OF DETERGENTS ON KERATINOCYTE GENE-EXPRESSION

We have studied the effect of various detergents on keratinocyte gene expression in vitro, using an anionic detergent (sodium dodecyl sulfat e), a cationic detergent cetyltrimethylammoniumbromide (CTAB), and two nonionic detergents, Nonidet P-40 and Tween-20. We measured the effec t of these detergents on direct cellular toxicity (lactate dehydrogena se release), on the expression of markers for normal differentiation ( cytokeratin I and involucrin expression), and on disturbed keratinocyt e differentiation (SKALP) by nothern blot analysis, As reported in oth er studies, large differences were noted in direct cellular toxicity. In a culture model that mimics normal epidermal differentiation we fou nd that low concentrations of sodium dodecyl sulfate could induce the expression of SKALP, a proteinase inhibitor that is not normally expre ssed in human epidermis but is found in hyperproliferative skin, Sodiu m dodecyl sulfate caused upregulation of involucrin and downregulation of cytokeratin 1 expression, which is associated with the hyperprolif erative/inflammatory epidermal phenotype found in psoriasis, wound hea ling, and skin irritation, These changes were not induced after treatm ent of cultures with CTAB, Triton X-100, and Nonidet-P40. This effect appeared to be specific far the class of anionic detergents because so dium dodecyl benzene sulfonate and sodium laurate also induced SKALP e xpression, These in vitro findings showed only a partial correlation w ith the potential of different detergents to induce clinical, biophysi cal, and cell biologic changes in vitro in human skin. Both sodium dod ecyl sulfate and CTAB were found to cause induction and upregulation o f SKALP and involucrin at low doses following a 24 h patch test, where as high concentrations of Triton X-100 did not, Sodium dodecyl sulfate induced higher rates of trans; epidermal water loss, whereas CTAB tre ated skin showed more signs of cellular toxicity, We conclude that the action of anionic detergents on epidermal keratinocytes is qualitativ ely different from the other detergents tested, which might have impli cations for in vitro toxicology studies that use cell biologic paramet ers as a read-out, We would hypothesize that detergents cause skin inj ury by several mechanisms that include direct cellular toxicity, disru ption of barrier function, and detergent specific effects on cellular differentiation, as demonstrated here for sodium dodecyl sulfate, sodi um dodecyl benzene sulfonate, and sodium laurate.