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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E2 (PGE2) is associated with phorbol ester-induced skin irritation and tumour promotion, but the mechanism of action is not fully understood and the role of keratinocyte-derived PGE2 is unclear. PGE2 was recently reported to modulate keratinocyte differentiation and phorbol-12-myristate-13-acetate (PMA), the most extensively studied phorbol ester tumour promoter in mouse skin, was shown to stimulate PGE2 release in human keratinocytes. Preliminary data on PGE2 release induced by PMA, mezerein, anthralin, sodium dodecyl sulphate and acetic acid in human keratinocyte cultures is compared to their response in rat keratinocytes. Our data confirms a previously published report on stimulation of PGE2 release by PMA in human keratinocytes and also demonstrates a difference in the magnitude of the PMA- and mezerein-induced response between human and rat keratinocyte cultures at non-cytotoxic concentrations. Cytotoxicity was evaluated by the Neutral Red uptake assay and a concentration that reduced cell viability to 50% of control was selected as a maximum concentration for subsequent measurement of PGE2 release. In contrast, anthralin, sodium dodecyl sulphate and acetic acid induced a similar degree of PGE2 release in human and rat keratinocyte cultures, but release was specifically associated with a cytotoxic response. Non-cytotoxic concentrations of these three chemicals did not stimulate release of PGE2. This study illustrates that PGE2 dose-response curves may reflect different mechanisms of action that may be intimately associated with skin irritant and tumour promoting activity. The data indicates a possible species difference in keratinocyte response to PMA and mezerein. The important value of keratinocyte cultures for mechanistic studies of tumour promotion and skin irritation is highlighted and further research is warranted into the potential role of intracellular pathways, which modulate keratinocyte differentiation and proliferation, in these processes.
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PMID:Comparison of tumour promoter-induced prostaglandin E2 release in human and rat keratinocytes. 776 93

Biochemical parameters of cytotoxicity, such as the release of intracellular enzymes, appear to be useful for classification of irritant substances following in vivo chemical insult to the skin. Changes in activity of acid phosphatase (AP), a lysosomal enzyme, appear to parallel the development of the inflammatory response in laboratory animals after treatment with the known skin irritant sodium dodecyl sulphate (SDS). Neutral red (NR) uptake and AP were chosen as endpoints of cytotoxicity. NR and AP were measured in cultures of human epidermal keratinocytes, prepared from separate individuals, and in 3T3 cells following treatment with SDS. The NR(50) value (concentration producing a 50% reduction in NR uptake compared with controls) was similar in both cell types. AP in human keratinocyte cultures exhibited a peak activity, before declining at higher concentrations. This phenomenon was time dependent and was observed within 4 hr of treatment, but was not evident after a 24-hr exposure. The peak produced in 3T3 cells was negligible in comparison. The rate of NR uptake was also studied within the first 4 hr of exposure to SDS, which was comparable to the earlier time points at which AP was determined. The degree of inhibition of NR uptake was greater in human keratinocyte cultures than in 3T3 cells and a response was also elicited at lower dose levels in keratinocytes. AP may be a sensitive indicator of cytotoxicity in human keratinocytes and the data may be interpreted in relation to changes in lysosomal membrane function. This assay may be of value in assessment of skin irritation potential of aqueous soluble surfactants and chemicals that possess the ability to damage biological membranes.
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PMID:Surfactant-induced cytotoxicity in cultures of human keratinocytes and a commercially available cell line (3T3). 2073 18