1. Laboratory of Toxicology, Department of Pharmacological Sciences, University of Milan, Italy
2. ^*Laboratory of Antioxidants, Department of Pharmacological Sciences, University of Milan, Italy
3. ^†Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA

Correspondence: Emanuela Corsini, PhD, Laboratory of Toxicology, Department of Pharmacological Sciences, Via Balzaretti 9, 20133 Milan, Italy; Email: emanuela.corsini@unimi.it

Received 20 December 2002; Revised 7 March 2003; Accepted 8 March 2003; Published online 23 July 2003.

Abstract

Keratinocytes play an important role in skin irritation. In an attempt to investigate mechanistic bases of human skin irritation response, we recently identified the upregulation by skin irritants of adipose differentiation related protein (ADRP) in reconstituted human epidermis. ADRP is a lipid-storage-droplet-associated protein, governing deposition and release of lipids from droplets. The purpose of this study was to characterize, in a human keratinocyte cell line (NCTC 2544), sodium-dodecyl-sulfate-induced ADRP expression, to identify the biochemical events that lead to ADRP expression, and to understand its function in sodium dodecyl sulfate cytotoxicity. Sodium dodecyl sulfate induced a concentration- and time-related production of ADRP that was associated with lipid droplet accumulation. Lipid accumulation following sodium dodecyl sulfate treatment was due to intracellular redistribution rather than lipid neosynthesis, as indicated by equivalent ¹⁴C-oleate and ¹⁴C-acetate incorporations. Other skin irritants, namely benzalkonium chloride, tributyltin, and 12-O-tetradecanoylphorbol 13-acetate, also induce lipid droplet accumulation. Sodium-dodecyl-sulfate-induced ADRP expression and lipid droplet accumulation were modulated by the calcium chelator BAPTA, indicating a role of calcium in ADRP induction. Decrease of sodium-dodecyl-sulfate-induced ADRP expression by specific ADRP antisense oligonucleotide resulted in increased cytotoxicity, indicating a protective role of ADRP and lipid accumulation in the process of cell damage induced by skin irritants. ADRP expression was also induced in vivo following treatment with sodium dodecyl sulfate in an experimental model of skin irritation, indicating that the in vitro model represents irritation.