Beneficial effects of tissue inhibitor of metalloproteinases-2 (TIMP-2) on chronic dermatitis.

Chronic dermatitis, such as contact dermatitis (CD) or atopic dermatitis (AD), is a longstanding inflammatory skin disease with cutaneous damage such as erosion, ulceration, and lichenification due to itch-induced scratching. The resultant lesion can be considered to be a kind of wound. The tissue inhibitor metalloproteases-2 (TIMP-2) accelerates wound healing by enhancing the proliferation and migration of epidermal keratinocytes and dermal fibroblasts; it is also a physiologic inhibitor of matrix metalloproteinases. The aim of this study was to test the effect of TIMP-2 on chronic dermatitis. NC/Kuj mice were sensitized with Dermatophagoides farinae (Df) extract. Eczema was induced by repeated applications of this mite allergen to the skin of 20 sensitized mice that were maintained under specific pathogen-free conditions. One group of 10 mice was then treated with topical TIMP-2 solution (0.1 ml, 0.5%) for 28 days, and the other with vehicle alone and the effects of TIMP-2 were evaluated macro- and microscopically. The effect on skin barrier function was estimated by measuring transepidermal water loss (TEWL). Scoring of gross skin findings showed that TIMP-2 significantly reduced the severity of eczema (P<0.05) on days 12-28. Histological examination revealed that TIMP-2 treated mice manifested lower degrees of hyperkeratosis, acanthosis, and spongiosis in the epidermis and fewer inflammatory cells in the dermis than vehicle-treated mice. There were significant reductions in the epidermal thickness and dermal inflammatory cells in the TIMP-2 treated animals (P<0.01); their TEWL was significantly decreased on day 28 (P<0.05). Our results suggest that NC/Kuj mice with Df extract-induced chronic eczema may be a useful model for investigating chronic dermatitis, and that TIMP-2 may be a good agent for treating chronic dermatitis as well as chronic ulcers.