Journal
DIGESTIVE AND LIVER DISEASE
Volume 42, Issue 8, Pages 544-548Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.dld.2009.12.005
Keywords
Crohn's disease; Peripheral blood mononuclear cells; Telomere binding proteins; Ulcerative colitis
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Funding
- Medical Research Council [G0501638] Funding Source: researchfish
- MRC [G0501638] Funding Source: UKRI
- Medical Research Council [G0501638] Funding Source: Medline
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Aims: To determine mRNA expression of telomeric binding proteins in inflammatory bowel disease (IBD), and to note any effects of pharmacotherapy on telomere binding protein expression. Methods: Peripheral blood mononuclear cells (PBMC) obtained from 31 IBD patients and 13 controls were activated with phytohaemagglutinin and purified to yield activated (CD25+)T lymphocytes. TPP1, POT1, RAP1,TRF1 and TRF2 mRNA expression in PBMC and activated T lymphocytes was measured with RT-PCR. Results: In activated (CD25+) T lymphocytes, mean TRF2 mRNA levels were lower in both UC (6.6 vs 10, p = 0.004) and CD subjects (6.9 vs 10; p = 0.004). Similarly, in activated (CD25+) T lymphocytes mean RAP1 mRNA expression was significantly lower in UC subjects (4.5 vs 9.8, p = 0.029) but not in CD subjects. In resting PBMC, mean TRF1 mRNA levels were lower in both UC (2.6 vs 3.5; p = 0.008) and CD subjects (1.0 vs 3.5; p = 0.04). No difference in PBMC and activated (CD25+) T lymphocytes mRNA levels of TPP1 and POT1 were noted in either UC or CD subjects. An association with 5-aminosalicylate therapy (R-2 =0.4) was only detected with RAP1 mRNA expression. TRF2 mRNA expression was inversely associated with disease duration only in UC subjects (p = 0.05; R-2 = 0.6). Conclusions: The downregulation of TRF2 and RAP1 mRNA expression in CD25+ T-lymphocytes in IBD suggests that these telomere binding proteins play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in UC. These findings may also indicate a systemic process of telomere uncapping which could represent a biomarker for IBD associated cancer risk. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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