Immunohistochemical Study of the Apoptotic and Proliferative Mechanisms in
the Intestinal Mucosa During Coeliac Disease
Lísová S.1, Ehrmann J.1 , Kolek A.2, Sedláková E.1, Kolář Z.1
1Ústav patologie LF UP a FN, Olomouc 2Dětská klinika FN, Olomouc |
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Summary:
yet completely recognized, however, two main processes have been suggested recently:
remodelling of mucosa by matrix metalloproteinases, and mucosal atrophy by apoptosis. The aim
of this study was to analyze the expression of proteins regulating apoptosis and some markers of
proliferation in the mucosa of the small intestine of children with active (ACD) and latent form
(LCD) of coeliac disease (CD). Intestinal biopsies of 43 children with ACD and LCD were analyzed
by standard indirect immunohistochemical technique for Fas, Fas ligand (Fas-L), tissue
transglutaminase (tTG), Bcl-2, Bid, glutathione S-transferase (GST), CAS 3, CAS 8, PARP, Ki-67,
Topoisomerase IIa, PCNA expression. We found significantly lower numbers of Fas-expressing
enterocytes in ACD patients than in LCD patients and controls. The number of Fas-positive
mucosal lymphocytes was decreased in ACD when compared with LCD. Fas-L expression in
enterocytes and mucosal lymphocytes was higher in ACD and LCD compared to controls.We found
significantly more Bcl-2 negative lymphocytes in ACD than in LCD and controls. Bid expression in
enterocytes was higher in LCD compared to ACD and controls. In intraepithelial lymphocytes,
there was higher Bid expression in LCD than in ACD and controls compared to expression in
mucosal lymphocytes, where was found higher number of positive cells in controls than in ACD
and LCD. Expression of CAS 8 in mucosal lymphocytes was significantly higher in ACD compared
to LCD. The expression of tTG in extracellular matrix and basal lamina was significantly higher in
LCD and ACD when compared to controls. Expression of tTG was higher in the group of ACD and
LCD in the enterocytes and in the lymphocytes. Our findings showed that Fas/Fas-L, Bcl-2, and CAS
8 may be involved in modulation of apoptosis during CD. Increased apoptotic elimination of IEL in
LCD can partially explain preservation of the normal villous architecture. Increased tTGexpression may be an early sign of increased apoptosis or may be related to its role in CD
pathogenesis.
Key words:
coeliac disease – apoptosis- Fas/Fas-L – Cas 3,8 – PARP
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