Expression of the Apoptotis Related Proteins in the Celiac Jejunal Mucosa
Kolek A.1, Ehrmann J. jr.2, Lísová S.2, Koďousek R.3, Drábek J.4, Heřmanová Z.4, Zapletalová J.5, Kolář Z.2
1 Dětská klinika 2 Laboratoř molekulární patologie 3 Ústav patologické anatomie 4 Imunologický ústav5 Ústav biofyziky FN a LF UP v Olomouci |
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Summary:
Aim: Villous atrophy of jejunal mucosa in celiac disease (CD) is mediated by the T cell reaction following the
gluten ingestion. It was suggested that this changes are due to excessive apoptotic enterocytes loss. The aim
was to analyse the expression of apoptosis regulating proteins in small intestine of patients with celiac
disease.
Patients and methods: Formalin fixed and paraffin embedded samples of jejunal mucosa of 25 untreated active
CD (ACD), 18 latent CD (LCD) and 21 controls were investigated. CD has been diagnosed according to
ESPGHAN criteria. A standard indirect immunohistochemical technique was used for Fas, Fas-L, caspase 3
and 8, tissue transglutaminase (tTG), Bcl-2, BID a PARP detection. Expression of proteins was scored semiquantitavely.
A two-way sample analysis and chi-square tests were used for statistics.
Results: The expression of Fas protein in enterocytes was significantly lower (p < 2 × 10-7) in ACD when
compared to the controls and to the LCD. Expression of CAS-8 was significantly higher (p < 0.04) in ACD and
controls compared to LCD. BID expression was highest in LCD compared to ACD and controls (p < 0,01). In
lamina propria lymphocytes was the Fas positivity in ACD significantly lower (p < 0.003) compared to LCD.
Fas-L expression was higher (p < 0.003) in ACD and LCD compared to controls. We found significantly more
(p < 0.005) Bcl-2 negative lymphocytes in ACD than in LCD and controls. BID expression was higher in ACD
compared to LCD and controls (p < 0.00001). Expression of tTG was higher in the group of ACD both in the enterocytes and in the lymphocytes. In intraepithelial lymphocytes was higher BID expression in LCD than in
ACD and controls (p < 0.02) and lower PARP expression in LCD compared to ACD and controls (p < 0.02).
Conclusions: Our findings indicate importance of Fas/Fas-L, Bcl-2 and other proteins in modulation of apoptosis
during CD. Increased apoptotic elimination of IEL in LCD can partially explain preservation of normal
villous architecture. Results of tTG expression require careful interpretation. Increased tTG expression may
be an early sign of increased apoptosis or may be related to its role in CD pathogenesis.
Key words:
celiac disease – apoptosis – Fas – Fas-L – CAS 3,8 – Bcl-2 – BID – PARP
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