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Alterations in the Composition of the Supramucosal Defense Barrier in Relation to Disease Severity of Ulcerative Colitis

Rob J. Longman, Richard Poulsom, Anthony P. Corfield, Bryan F. Warren, Nicholas A. Wright and Michael G. Thomas

University Departments of Surgery (RJL,MGT) and Medicine (APC), Bristol Royal Infirmary, Bristol, United Kingdom; Histopathology Unit, Cancer Research UK, London, United Kingdom (RP,NAW); Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom (BFW); and School of Medicine and Dentistry, Barts and The London, London,United Kingdom (NAW)

Correspondence to: Mr. R.J. Longman, BSc, PhD, MBChB, FRCS (Gen Surg), c/o Mr. M.G. Thomas, Consultant Colorectal Surgeon, Colorectal Surgery Unit, Level 4, Bristol Royal Infirmary, Bristol BS2 8HW, UK. E-mail: rob.longman{at}blueyonder.co.uk

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease. (J Histochem Cytochem 54:1335–1348, 2006)

Key Words: ulcerative colitis • mucin glycoproteins • trefoil peptides • immunohistochemistry • in situ hybridization

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