Parallel expression of macrophage metalloelastase (MMP-12) in duodenal and skin lesions of patients with dermatitis herpetiformis.
BACKGROUND
Dermatitis herpetiformis (DH) is a specific dermatological manifestation of coeliac disease and 80% of DH patients have gluten sensitive enteropathy manifested by crypt hyperplasia and villous atrophy. Matrix degradation mediated by collagenase 1 (MMP-1) and stromelysin 1 (MMP-3) has previously been implicated in the pathobiology of coeliac intestine and cutaneous DH blisters.


OBJECTIVE
To study expression of stromelysin 2, metalloelastase, collagenase 3, and matrilysin in the intestine and skin of DH patients.


METHODS
In situ hybridisation using 35S labelled cRNA probes was performed on duodenal biopsies of 15 DH patients, three samples each of control duodenal or jejunal mucosa, fetal ileal explants, lesional DH skin, and 19 serial biopsies of experimental DH blisters. Immunostaining was used to examine type IV collagen, macrophages (CD68), and 92 kDa gelatinase (MMP-9) in the specimens.


RESULTS
Metalloelastase (MMP-12) was abundantly expressed by subepithelial macrophages in both coeliac intestine and spontaneous and induced DH rash. It was also upregulated in the experimental model of coeliac disease (staphylococcal endotoxin B stimulated fetal explants). The only other MMP detected was MMP-9 which did not colocalise with MMP-12.


CONCLUSIONS
Upregulation of metalloelastase is associated with T cell mediated immune responses both in the intestine and skin. In addition to modulating macrophage migration, it may contribute to degradation of proteoglycans or basement membrane components in the subepithelial mucosa.
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
M T
MT
Salmela
S L
SL
Pender
T
T
Reunala
T
T
MacDonald
U
U
Saarialho-Kere
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003874:Dermatitis Herpetiformis / Q000201:enzymology*; D004386:Duodenum / Q000201:enzymology*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D018075:RNA, Complementary; D012867:Skin / Q000201:enzymology*; D015854:Up-Regulation
D018075:RNA, Complementary; D003094:Collagen; D017364:Collagenases; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9