Article Text
Abstract
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.
AIMS 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.
- coeliac disease
- metalloproteinase
- dermatitis herpetiformis
Abbreviations used in this paper
- DH
- dermatitis herpetiformis
- MMPs
- matrix metalloproteinases
- BM
- basement membrane
- CD
- coeliac disease
- ECM
- extracellular matrix
- SEB
- staphylococcal endotoxin B
- tTG
- tissue transglutaminase
- IFN-γ
- interferon γ
- IL
- interleukin
- TNF-α
- tumour necrosis factor α
- TGF-β
- transforming growth factor β
- GM-CSF
- granulocyte macrophage-colony stimulating factor
Statistics from Altmetric.com
Abbreviations used in this paper
- DH
- dermatitis herpetiformis
- MMPs
- matrix metalloproteinases
- BM
- basement membrane
- CD
- coeliac disease
- ECM
- extracellular matrix
- SEB
- staphylococcal endotoxin B
- tTG
- tissue transglutaminase
- IFN-γ
- interferon γ
- IL
- interleukin
- TNF-α
- tumour necrosis factor α
- TGF-β
- transforming growth factor β
- GM-CSF
- granulocyte macrophage-colony stimulating factor