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Expression of apoptosis-related proteins in rat with induced colitis

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Inflammatory bowel diseases (IBD) evoke a damage-repair process accompanied by the activation of apoptotic genes. Data on transglutaminase (TG) expression in apoptotic cells in inflamed colonic epithelium has not been reported, although TG cross-links proteins within typical apoptotic bodies in various cell lines. In an experimental model of colitis we investigated the expression of different markers of apoptosis related to the degree and development of colonic inflammation.

Methods

Two studies were performed: (a) Colitis was induced by the administration of 2,4,6-trinitrobenzen sulfonic acid (TNBS) at a dose of 10 or 20 mg per rat in 50% ethanol, and the rats were killed 1 week later; (b) Colitis was induced by 20 mg TNBS and the rats were killed 3 days, 1, 2, and 4 weeks thereafter. The colon of rats was macroscopically assessed, and biopsies were histologically assessed and immunoprobed for FasL, FasR, p53 and tTG. Cell death was detected by TUNEL, and TG activity was assayed on colon homogenates.

Results

Study A: According to enhanced TUNEL positivity, FasR/FasL and p53 expression increased depending on the severity of the colitis. Study B showed increased p53 expression at day 3 while FasR/FasL coexpression peaked at 1 week. In both studies tTG was mainly expressed in the extracellular matrix of damaged tissue and in the submucosa.

Conclusions

Our findings suggest that expression of apoptosis markers is related to the degree of colitis and show that apoptosis is sustained by both p53 and FasR/FasL pathways, depending on the phase of colitis development. Moreover, the lack of TG staining in typical apoptotic bodies may account for a perturbation of the cross-linked apoptotic envelope that may be an important determinant in the development of immune response in ulcerative colitis.

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Authors and Affiliations

  1. Cattedra di Gastroenterologia, Facoltà di Medicina, Università di Napoli Federico II, Via Pansini 5, 80131Napoli, Italy

    Giuseppe D’Argenio, Vittorio Cosenza, Francesca De Ritis, Nicola Della Valle & Francesco Manguso

  2. Dipartimento di Biologia, Università di Tor Vergata, Rome, Italy

    Maria Grazia Farrace & Mauro Piacentini

Authors
  1. Giuseppe D’Argenio
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  2. Maria Grazia Farrace
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  3. Vittorio Cosenza
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  4. Francesca De Ritis
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  5. Nicola Della Valle
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  6. Francesco Manguso
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  7. Mauro Piacentini
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Correspondence to Giuseppe D’Argenio.

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D’Argenio, G., Farrace, M.G., Cosenza, V. et al. Expression of apoptosis-related proteins in rat with induced colitis. Int J Colorectal Dis 19, 451–460 (2004). https://doi.org/10.1007/s00384-004-0585-5

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