New Approaches Towards the Elucidation of Epidermal-Dermal Separation in Sulfur Mustard-Exposed Human Skin and Directions for Therapy
Abstract
Microvesication in human skin, due to ex viva exposure to HD, can be blocked by 1) hydroxamate-based inhibitors of MMPs and related enzymes, 2) furin inhibitor and 3) pancaspase inhibitor. The observation that one of the hydroxamate-based inhibitors, BB94, can be applied until 18h after exposure to HD suggests that non-urgent cure of HD casualties is possible. During pathogenesis of HD-induced microvesication the expression of laminin-5, one of the key proteins in epidermal dermal attachment, is reduced. However, although laminin-5 is target protein for MMps and related enzymes, these enzymes are not responsible for the decrease in laminin-5 expression. Moreover, epidermal-dermal attachment is still possible, in spite of reduced amounts of laminin-5. Cleavage of other attachment proteins than laminin-5 by MMps and related enzymes probably causes the break between epidermis and dermis. Impediment of the apoptotic cell death process appears to be also very effective in maintaining epidermal-dermal adhesion. The observation that caspase inhibitors prevent fragmentation of keratins 14, 16, and 17 in HD-exposed HEK may suggest that an intact cytoskeleton of keratin filaments is essential for epidermal-dermal adhesion. The observation that caspase inhibitors prevent fragmentation of keratins 14, 16, and 17 in HD-exposed HEK may suggest that an intact cytoskeleton of keratin filaments is essential for epidermal-dermal attachment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423257
Entities
People
- Marijke A. Mol
Organizations
- Prins Maurits Laboratorium TNO