Surg Today (2006) 36:287–290 DOI 10.1007/s00595-005-3144-y Short Communication The Expression Patterns of Toll-Like Receptors in the Ileal Pouch Mucosa of Postoperative Ulcerative Colitis Patients Yuji Toiyama, Toshimitsu Araki, Shigeyuki Yoshiyama, Jun-ichiro Hiro, Chikao Miki, and Masato Kusunoki Second Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan pouches of 100 : 1, compared to 4 : 1 in ileostomy effluent, has been noted, and observations suggesting that anaerobes play a role in this etiology thus require further study. 3 The Toll-like receptor (TLR) family comprises at least eight human homologues of the Drosophila Toll protein which appear to be key regulators in the differ- ential cellular recognition of conserved molecular pat- terns associated with microbial pathogens. 4 Among this family, TLR2 and TLR4 have been most extensively studied to date, and these studies have variably sug- gested that both TLRs may serve as potential main mediators of lipopolysaccharide (LPS) signaling. 5 Alexopoulou et al. 6 demonstrated that viral dsRNA recognition relies on the TLR3, and Flagellin, a patho- gen-associated molecular pattern (PAMP), has been identified as the specific ligand for TLR5. We speculate that an immune imbalance in pouchitis might result from an exaggerated activation of the mucosal innate immune system in response to the bacterial products of the lumen initiated through the dysregulation of TLRs. However, it remains unclear as to whether TLRs are expressed in the ileum mucosa in vivo and how such expression may be altered in the pouch mucosa either with or without inflammation. The aim of this study was thus to evaluate the expression of various PAMP receptors TLR2, -3, -4, and -5 in the pouch mucosa of postoperative UC patients in compari- son with those in normal controls. Biopsy samples were obtained from three patients diagnosed to have pouchitis (3 months, 16 months, and 24 months after undergoing ileoanal anastomosis). After a total proctocolectomy with a diverting ileo- stomy, noninflamed pouch mucosa specimens from five patients were also collected. Normal ileal mucosa speci- mens were obtained from five patients with ascending colon cancer who underwent surgery at Mie University Hospital. Informed consent was obtained from each patient. Abstract The aim of this study was to evaluate the expression pattern of Toll-like receptors (TLRs) in the pouch mu- cosa of ulcerative colitis patients in comparison with that in the ileum mucosa of noninflammatory bowel disease patients. Pouch mucosal biopsy specimens were collected from postoperative patients who had under- gone surgery for ulcerative colitis. Normal ileum speci- mens were collected from colon cancer patients. The specimens were assessed by immunofluorescence his- tochemistry using TLR2, TLR3, TLR4, and TLR5 polyclonal antibodies. The normal ileal mucosa consti- tutively expressed TLR3 and TLR5, whereas TLR2 and TLR4 were barely detectable. In the mucosa of active pouchitis, TLR2 and TLR4 was strongly upregulated, and TLR4 was upregulated even in a noninflamed pouch. No TLR3 or TLR5 expression was detectable. These data suggest that pouchitis may be associated with distinctive changes in selective TLR expression in the pouch mucosa, and that TLR4 alterations in the innate response system may contribute to the pathogen- esis of these disorders in particular. Key words Pouchitis · Toll-like receptor · Ulcerative colitis The current treatment of choice for many patients re- quiring a colectomy for ulcerative colitis (UC) or famil- ial adenomatous polyposis is ileoanal anastomosis with pouch creation. The symptomatic inflammation of the pouch, a condition known as pouchitis, develops in from 7% to 40% of all patients who undergo this surgery. 1 At the present time, no clear microbiologic factor has been shown to play a part in the etiology. 2 However, a marked increase in the anaerobe/aerobe ratio in Reprint requests to: M. Kusunoki Received: February 3, 2005 / Accepted: July 12, 2005