Therapeutic relevance of inhibitors of MMPs or of caspases in HD-induced injury in the ex vivo human skin model
conference paper
In order to prevent microvesication, direct and indirect inhibitors of matrix metalloproteases (MMPs) can be used to fully prevent HD-induced epidermal-dermal separation in organ-cultured human skin pieces. The MMP inhibitors show no effect on the massive epidermal cell damage caused by HD. Interestingly, a pancaspase inhibitor causes a reduction in the number of dead keratinocytes and blocks microvesication as well. Furthermore, it is shown that application of the MMP inhibitor BB94 to the culture medium as late as 18 h after exposure to HD is still effective. The fate of laminin-5, one of the BM proteins, has been studied immunohistochemically. The expression of laminin-5 is reduced in HD-exposed skin. However, in the presence of BB94 or of pancaspase inhibitor, no improvement of laminin-5 immunostaining is observed, although microvesication is absent. Reduced expression of laminin-5 seems to be not the main cause of microvesication. It is concluded that conservation of BM proteins other than laminin-5 either by inhibiting degradation by MMPs or by preserving epidermal cell protein production is critical in therapeutic treatment of HD-induced microvesication in an ex vivo human skin model.
TNO Identifier
526867
Source title
Bioscience 2004 "Medical Chemical Defense Research for the Warfighter and Homeland Defense", US Army Medical Defense Bioscience Review, 18-21 May 2004
Collation
9 p.
Pages
Chapter 222
Files
To receive the publication files, please send an e-mail request to TNO Repository.