Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of various detergents on keratinocyte gene expression in vitro, using an anionic detergent (sodium dodecyl sulfate), a cationic detergent cetyltrimethylammoniumbromide (CTAB), and two nonionic detergents, Nonidet P-40 and Tween-20. We measured the effect of these detergents on direct cellular toxicity (lactate dehydrogenase release), on the expression of markers for normal differentiation (cytokeratin 1 and involucrin expression), and on disturbed keratinocyte differentiation (SKALP) by northern blot analysis. As reported in other studies, large differences were noted in direct cellular toxicity. In a culture model that mimics normal epidermal differentiation we found that low concentrations of sodium dodecyl sulfate could induce the expression of SKALP, a proteinase inhibitor that is not normally expressed in human epidermis but is found in hyperproliferative skin. Sodium dodecyl sulfate caused upregulation of involucrin and downregulation of cytokeratin 1 expression, which is associated with the hyperproliferative/inflammatory epidermal phenotype found in psoriasis, wound healing, and skin irritation. These changes were not induced after treatment of cultures with CTAB, Triton X-100, and Nonidet-P40. This effect appeared to be specific for the class of anionic detergents because sodium dodecyl benzene sulfonate and sodium laurate also induced SKALP expression. These in vitro findings showed only a partial correlation with the potential of different detergents to induce clinical, biophysical, and cell biologic changes in vivo in human skin. Both sodium dodecyl sulfate and CTAB were found to cause induction and upregulation of SKALP and involucrin at low doses following a 24 h patch test, whereas high concentrations of Triton X-100 did not. Sodium dodecyl sulfate induced higher rates of transepidermal water loss, whereas CTAB treated skin showed more signs of cellular toxicity. We conclude that the action of anionic detergents on epidermal keratinocytes is qualitatively different from the other detergents tested, which might have implications for in vitro toxicology studies that use cell biologic parameters as a read-out. We would hypothesize that detergents cause skin injury by several mechanisms that include direct cellular toxicity, disruption of barrier function, and detergent specific effects on cellular differentiation, as demonstrated here for sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, and sodium laurate.
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PMID:Differential effects of detergents on keratinocyte gene expression. 954 Sep 75

Topical administration of triptolide (TP) is effective in the treatment of rheumatoid arthritis (RA), but it can also induce skin irritation. Previous studies have used data mining strategies to analyze the application of Tripterygium wilfordii in the treatment of RA and have shown that TP and ferulic acid (FA) can be used in combination due to their component compatibility. The aims of the present study were to investigate the mechanisms underlying the effects of TP treatment and to identify its effects on metabolism and oxidative damage in the skin. MTT assay results suggested that the HaCaT cell survival rate was significantly increased when the compatibility ratio of TP to FA was 1:100. Moreover, the combination of TP with FA (TP + FA) did not significantly affect the activities of the cytochrome P40 (CYP) enzymes CYP family 1 subfamily A member 2 (CYP1A2), CYP2E1 and CYP3A4, when used as a 'cocktail'. It was found that TP + FA significantly decreased the production levels of reactive oxygen species (ROS), superoxide dismutase and malondialdehyde in HaCaT cells, while significantly increasing levels of glutathione and catalase. In addition, TP + FA significantly increased nuclear factor erythroid 2-related factor 2 protein expression, compared with TP alone. Thus, the present results indicated that the underlying mechanism of TP + FA efficacy may be related to decreased ROS production level in HaCaT cells, increased production levels of key antioxidant factors and increased antioxidant activity of the epidermis, all of which were correlated with a protective effect against oxidative damage.
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PMID:Influence of a combination of triptolide and ferulic acid on the activities of CYP450 enzymes and oxidative stress in HaCaT cells. 3309 95