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

Abstract

In skin biology, matrix metalloproteinases (MMPs) have been implicated in inflammatory matrix remodeling, neovascularization, wound healing and malignant transformation. Psoriasis is histologically characterized by keratinocyte hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-alpha, IL-1beta, TGF-alpha, and IFN-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, in psoriasis, we performed in situ hybridization using 35S-labeled cRNA probes on 29 psoriatic lesions and 9 samples of normal looking skin from psoriatic patients. Metalloelastase mRNA was detected in 21/27 samples in macrophages that had migrated into the epidermis or in the inflammatory infiltrates of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in basal keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in basal keratinocytes of the same samples, suggested that stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for stromelysin-2 or collagenase-3 was found and only sweat glands were positive for matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the inflammatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP-3 was expressed perivascularly in 9/16 samples. Our results suggest that overexpression of the investigated MMPs by keratinocytes is not associated with psoriasis. However, macrophages express MMPs in psoriatic skin. Also TIMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

“…Since MMP-12 is not only involved in lung tissue remodeling-associated diseases [35,37,41,46,50,[81][82][83][84][85][86][87][88][89], substantial efforts have been made to develop MMP-12 synthetic inhibitors. However, inhibiting a specific MMP is a difficult goal because of the high conservation between many MMPs in terms of overall 3D-structure, topology of the catalytic domain and requirement of specific amino-acid residues in the active site [90,91].…”

Systemic treatment and narrowband ultraviolet B differentially affect cardiovascular risk markers in psoriasis

“…25 The MMP9 protein is induced by TNF-α and is in psoriatic lesions produced by macrophages and neutrophils. 26 In a study of psoriatic arthritis, infliximab treatment led to a reduction in the MMP9 and sE-selectin serum levels, together with a reduction in the spontaneous release of MMP9 and sE-selectin from lesional skin. 27 Therapy with TNF-α inhibitor also leads to a reduction in MMP9 in peripheral blood mononuclear cells, plasma and in psoriatic lesions.…”

From anti‐p200 pemphigoid to anti‐laminin γ1 pemphigoid

“…22 A previous report showed that laminin c1 from laminin 511 can be degraded by MMP-9, 23 which is highly expressed in the psoriatic skin lesions. 22 Increase of laminin c1 fragments that are processed by MMP-9 in psoriatic lesions may initiate the production of anti-laminin c1 autoantibody, which binds to the essential site for molecular interaction in the basement membrane zone of the skin. Several lines have suggested that expression of integrins is modified in the basement membrane zone of psoriatic skin.…”