Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease

Initiation and perpetuation of the inflammatory intestinal responses in inf lammatory bowel disease (IBD) may result from an exaggerated host defense r eaction of the intestinal epithelium to endogenous lumenal bacterial flora. Intestinal epithelial cell lines constitutively express several functional Toll like receptors (TLRs) which appear to be key regulators of the innate response system. The aim of this study was to characterize the expression pattern of TLR2, TLR3, TLR4, and TLR5 in primary intestinal epithelial cell s from patients with IBD. Small intestinal and colonic biopsy specimens wer e collected from patients with IBD (Crohn's disease [CD], ulcerative coliti s [UC]) and controls. Non-IBD specimens were assessed by immunofluorescence histochemistry using polyclonal antibodies specific for TLR2, TLR3, TLR4, and TLR5. Primary intestinal epithelial cells (IEC) of normal mucosa consti tutively expressed TLR3 and TLR5, while TLR2 and TLR4 were only barely dete ctable. In active IBD, the expression of TLR3 and TLRL4 was differentially modulated in the intestinal epithelium. TLR3 was significantly downregulate d in IEC in active CD but not in UC. In contrast, TLR4 was strongly upregul ated in both UC and CD. TLR2 and TLR5 expression remained unchanged in IBD. These data suggest that IBD may be associated with distinctive changes in selective TLR expression in the intestinal epithelium, implying that altera tions in the innate response system may contribute to the pathogenesis of t hese disorders.