Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease.
OBJECTIVE
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.
Da-Silva
Nancy
N
Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Clifford Bridge Rd, Coventry, CV2 2DX, UK.
Arasaradnam
Ramesh
R
Getliffe
Katherine
K
Sung
Edward
E
Oo
Ye
Y
Nwokolo
Chuka
C
D001379:Azathioprine / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D043171:Chromosomal Instability / Q000187:drug effects / Q000235:genetics; D003093:Colitis, Ulcerative / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008213:Lymphocyte Activation / Q000187:drug effects; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000089804:Shelterin Complex; D013601:T-Lymphocytes / Q000502:physiology; D016615:Telomere / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D034501:Telomere-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D035341:Telomeric Repeat Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics*
C495876:ACD protein, human; D014408:Biomarkers, Tumor; C440849:POT1 protein, human; D012333:RNA, Messenger; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D019804:Mesalamine; D001379:Azathioprine