Mt. Salmela et al., Parallel expression of macrophage metalloelastase (MMP-12) in duodenal andskin lesions of patients with dermatitis herpetiformis, GUT, 48(4), 2001, pp. 496-502
Background-Dermatitis herpetiformis (DH) is a specific dermatological manif
estation of coeliac disease and 80% of DH patients have gluten sensitive en
teropathy manifested by crypt hyperplasia and villous atrophy. Matrix degra
dation mediated by collagenase 1 (MMP-1) and stromelysin 1 (MMP-3) has prev
iously been implicated in the pathobiology of coeliac intestine and cutaneo
us 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 S-35 labelled cRNA probes was performed
on duodenal biopsies of 15 DH patients, three samples each of control duod
enal or jejunal mucosa, fetal ileal explants, lesional DH skin, and 19 seri
al 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 (staph
ylococcal endotoxin B stimulated fetal explants). The only other MMP detect
ed was MMP-9 which did not colocalise with MMP-12.
Conclusions-Upregulation of metalloelastase is associated with T cell media
ted immune responses both in the intestine and skin. In addition to modulat
ing macrophage migration, it may contribute to degradation of proteoglycans
or basement membrane components in the subepithelial mucosa.