Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, TIMP-1 and-3, are expressed in psoriatic lesions

In skin biology, matrix metalloproteinases (MMPs) have been implicated in i nflammatory matrix remodeling, neovascularization, wound healing and malign ant transformation. Psoriasis is histologically characterized by keratinocy te hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-alpha, IL-1 beta, TGF-alpha, and I FN-gamma, also capable of regulating MMP transcription. To investigate the role of stromelysins-1 and -2, matrilysin, metalloelastase, collagenases-1 and -3 and 92-kDa gelatinase as well as their inhibitors, TIMPs-1 and -3, i n psoriasis, we performed in situ hybridization using S-35-labeled cRNA pro bes on 29 psoriatic lesions and 9 samples of normal looking skin from psori atic patients. Metalloelastase mRNA was detected in 21/27 samples in macrop hages that had migrated into the epidermis or in the inflammatory infiltrat es of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in bas al keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in b asal keratinocytes of the same samples, suggested that stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for stro melysin-2 or collagenase-3 was found and only sweat glands were positive fo r matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the infla mmatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP- 3 was expressed perivascularly in 9/16 samples. Our results suggest that ov erexpression of the investigated MMPs by keratinocytes is not associated wi th 2 psoriasis. However, macrophages express MMPs in psoriatic skin. Also T IMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.