New Approaches Towards the Elucidation of Epidermal-Dermal Separation in Sulfur Mustard-Exposed Human Skin and Directions For Therapy
Abstract
The first year of the research performed under Award Number DAMD17-02-02O6 has yielded promising results. with respect to the application of MMP inhibitor BB94 on HD-exposed human skin pieces in order to prevent microvesication. BB94 is effective at a concentration of at least 1 mug/ml and can be added to the culture medium as late as 8 h after exposure to HD, without loosing its inhibiting effect on epidermal-dermal separation. From a therapeutic angle, this time window might allow non-urgent cure of HD casualties. In an adjacent series of experiments, application of proteomic analysis as an unbiased way to study cellular events following HD-exposure has proven to be a valuable approach. 2D-PAGE analysis of the protein profile of cultured HEK that were exposed to 100 muM HD gave clues for the induction of apoptosis by the gradual appearance over 24 h of fragments of the type I keratins K14 and K17, generated by caspase cleavage. It is expected that the identification of several other new spots that appeared in the protein pattern of HD-exposed HEK might shed more light on the mechanistic toxicology of HD. The results obtained in this study so far, suggest a dual treatment of HD-exposed skin: application of a MMP- inhibitor to prevent microvesication together with the use of a caspase-inhibitor to reduce epidermal cell damage.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA417385
Entities
People
- Marijke A. E. Mol
Organizations
- Prins Maurits Laboratorium TNO