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  • Parallel expression of macrophage metalloelastase (MMP-12) in duodenal and skin lesions of patients with dermatitis herpetiformis

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Small bowel
Parallel expression of macrophage metalloelastase (MMP-12) in duodenal and skin lesions of patients with dermatitis herpetiformis

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

    • https://doi.org/10.1136/gut.48.4.496

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