Modulation of Irritation-Induced Increase of E-selectin mRNA In Vivo by Topically Applied Corticosteroids

• Published in: Journal of investigative dermatology Vol. 113; no. 2; pp. 170 - 174
• Main Authors: KUKUTSCH, N. A, COORS, E. A, GRUSCHWITZ, M. S, VON DEN DRIESCH, P
• Format: Journal Article
• Language: English
• Published: Danvers, MA Nature Publishing 01.08.1999
• Subjects: Administration, Topical; Adult; Anti-Inflammatory Agents - administration & dosage; Biological and medical sciences; Biopsy; Dermatitis - genetics; Drug Eruptions - etiology; E-Selectin - genetics; Female; Humans; Hydrocortisone - therapeutic use; Male; Medical sciences; Pharmacology. Drug treatments; Prednisolone - administration & dosage; Prednisolone - analogs & derivatives; Prednisolone - therapeutic use; Premedication; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Skin - pathology; Skin, nail, hair, dermoskeleton; Sodium Dodecyl Sulfate - adverse effects; Triamcinolone - therapeutic use; Up-Regulation; Human; Corticosteroid; Local administration; Skin disease; Antiinflammatory agent; Skin; Experimental study; Biological activity; Irritation; Percutaneous route
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.1999.00660.x

There is a continuous need for methods to evaluate the biologic effects of topically applied drugs in the skin. Irritation of the epidermis with sodium dodecyl sulfate leads to an upregulation of E-selectin on endothelial cells and E-selectin mRNA can be detected in vivo within a short time. This study was aimed to investigate whether this biologic response can be used as a read-out for the anti-inflammatory effect of topically administered corticosteroids. We investigated skin of healthy volunteers treated according to the two following experimental protocols: (i) topical application of different corticosteroids (versus basic ointments as controls) for 12 h and irritation with sodium dodecyl sulfate 1% for 4 h; (ii) irritation with sodium dodecyl sulfate 1% for 12 h and application of the corticosteroids for 5 h. The biopsy specimens were subjected to RNA extraction and reverse transcription and competitive reverse transcriptase-polymerase chain reaction was performed using defined concentrations of a pre-constructed mimic DNA. As result, we found strong positive signals for wild-type E-selectin mRNA in all biopsies pretreated with basic ointments, whereas in biopsies from areas pretreated with corticosteroids the bands for wild-type E-selectin DNA could be detected at 10-1000 lower levels of mimic DNA concentrations. The reverse experiment, application of corticosteroids after the irritation, again yielded significantly reduced signals for E-selectin mRNA. In both experimental settings, the different strength of the topical corticosteroids used was reflected by significant differences in the amount of E-selectin mRNA found in the biopsies. This study demonstrates the pharmacologic effect of topical corticosteroids on the irritation-induced E-selectin mRNA expression on dermal endothelial cells in vivo using very small tissue samples and this approach may be of value for further pharmaceutical studies.