Urokinase Plasminogen Activator Is Expressed By Basal Keratinocytes Before Interstitial Collagenase, Stromelysin-1, and Laminin-5 in Experimentally Induced Dermatitis Herpetiformis Lesions

• Published in: Journal of investigative dermatology Vol. 108; no. 1; pp. 7 - 11
• Main Authors: Airola, Kristiina, Reunala, Timo, Salo, Sirpa, Saarialho-Kere, Ulpu K.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.01.1997; Nature Publishing
• Subjects: Biological and medical sciences; bullous disease; Bullous diseases of the skin; Collagen - biosynthesis; Collagenases - genetics; Dermatitis Herpetiformis - genetics; Dermatitis Herpetiformis - metabolism; Dermatology; Humans; Immunohistochemistry; In Situ Hybridization; Keratinocytes - chemistry; Laminin - genetics; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3 - genetics; Medical sciences; metalloproteinase; RNA, Messenger - analysis; Time Factors; Urokinase-Type Plasminogen Activator - genetics; metalloproteinase; bullous disease; Bullous dermatosis; Human; Immunohistochemistry; Immunopathology; Skin disease; Stromelysin 1; u-Plasminogen activator; Serine endopeptidases; Enzyme; Autoimmune disease; Metalloendopeptidases; Dermatitis herpetiformis; Basement membrane; Peptidases; Experimental disease; Laminin; Hydrolases; Keratinocyte; Interstitial collagenase
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12285610

We studied the temporal expression of interstitial collagenase, stromelysin-1 and -2 and urokinase plasminogen activator (uPA) mRNAs by in situ hybridization in eight patients with dermatitis herpetiformis. To induce blisters, 50% potassium iodide patch tests were performed and serial biopsy specimens were taken at 4, 12 and 24 h. Additional samples were taken from occasional spontaneous blisters. Components of the basement membrane, laminin-5, laminin-1 and type VII collagen, were examined immunohistochemically in relation to matrix metalloproteinase expression. At 12 h, when no blisters were seen, uPA mRNA was present in basal keratinocytes in five of eight samples, whereas interstitial collagenase and stromelysin-1 mRNA were not detected. At this time, immunohistochemistry failed to show changes in the basement membrane. At 24 h, uPA, collagenase and stromelysin-1 mRNAs were present in basal keratinocytes, suggesting an activation of latent forms of the two latter enzymes by the uPA-plasmin pathway. Signal for stromelysin-2 was not detected. Furthermore, disruptions of laminin-1 and type VII collagen were evident. The data suggest that stromelysin-1 and interstitial collagenase may contribute to the degradation of basement membrane in dermatitis herpetiformis. Intracellular staining for laminin-5 co-localized with collagenase mRNA in basal keratinocytes. Because laminin-5 is essential for adhesion of keratinocytes to basement membrane and for establishment of focal adhesions on migrating cells, its production may reflect a regenerative response after the destruction of basement membrane components.