title: Immunohistochemical study of the apoptotic mechanisms in the intestinal mucosa during children's coeliac disease.
abstract: Mechanisms leading to morphological changes of the small intestine during coeliac disease (CD) are not yet completely recognized; however, two main processes have been suggested recently: remodeling of mucosa by matrix metalloproteinases, and mucosal atrophy by apoptosis. The aim of this study was analysis of the expression of proteins regulating apoptosis in the small intestine of children with active CD (ACD) and potential CD (PCD). Jejunal biopsies of 43 children with PCD and untreated ACD and 21 control samples were analyzed by means of standard indirect immunohistochemical technique for Fas, Fas ligand (Fas-L), tissue transglutaminase (tTG), Bcl-2, and glutathione S-transferase (GST) expression. We found significantly lower numbers of Fas-expressing enterocytes in the ACD patients than in PCD patients and controls. Similarly, the number of Fas-positive mucosal lymphocytes was decreased in ACD when compared with PCD. The number of Fas-L- and tTG-expressing enterocytes and mucosal lymphocytes was higher in both PCD and ACD. On the other hand, the number of Bcl-2-positive mucosal lymphocytes in PCD as well as ACD was significantly lower. The expression of tTG in extracellular matrix was significantly higher in PCD and ACD when compared with controls. Our results showed that Fas and/or Fas-L, Bcl-2, and tTG may be involved in apoptotic pathways leading to mucosal atrophy in children with CD. tTG changes are in agreement with the presumed role of this protein in the pathogenesis of CD.
authors.affiliation: Laboratory of Molecular Pathology & Institute of Pathology, Palacký University, Hnevotínská 3 77515, Olomouc, Czech Republic.
authors.forename: Jirí
authors.initials: J
authors.lastname: Ehrmann
authors.forename: Antonín
authors.initials: A
authors.lastname: Kolek
authors.forename: Rostislav
authors.initials: R
authors.lastname: Kod'ousek
authors.forename: Jana
authors.initials: J
authors.lastname: Zapletalová
authors.forename: Sona
authors.initials: S
authors.lastname: Lísová
authors.forename: Paul Gerard
authors.initials: PG
authors.lastname: Murray
authors.forename: Jirí
authors.initials: J
authors.lastname: Drábek
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kolár
mesh_terms: D017209:Apoptosis; D001284:Atrophy; D001706:Biopsy; D002446:Celiac Disease / Q000378:metabolism / Q000473:pathology*; D002648:Child; D020895:Enterocytes / Q000737:chemistry; D053222:Fas Ligand Protein; D019204:GTP-Binding Proteins / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000473:pathology*; D007583:Jejunum / Q000737:chemistry / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000032:analysis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011503:Transglutaminases / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D005982:Glutathione Transferase; D019204:GTP-Binding Proteins