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Infection and Immunity, December 2000, p. 7010-7017, Vol. 68, No. 12
Gastrointestinal Unit, Massachusetts General
Hospital, and Harvard Medical School, Center for the Study of
Inflammatory Bowel Disease, Boston, Massachusetts 02114
Received 20 June 2000/Returned for modification 22 August
2000/Accepted 7 September 2000
Initiation and perpetuation of the inflammatory intestinal
responses in inflammatory bowel disease (IBD) may result from an exaggerated host defense reaction 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 cells from
patients with IBD. Small intestinal and colonic biopsy specimens were
collected from patients with IBD (Crohn's disease [CD], ulcerative
colitis [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 constitutively expressed TLR3 and TLR5, while
TLR2 and TLR4 were only barely detectable. In active IBD, the
expression of TLR3 and TLR4 was differentially modulated in the
intestinal epithelium. TLR3 was significantly downregulated in IEC in
active CD but not in UC. In contrast, TLR4 was strongly upregulated 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
alterations in the innate response system may contribute to the
pathogenesis of these disorders.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Differential Alteration in Intestinal Epithelial
Cell Expression of Toll-Like Receptor 3 (TLR3) and TLR4 in Inflammatory
Bowel Disease
*
Corresponding author. Mailing address: Massachusetts
General Hospital, Gastrointestinal Unit GRJ719, 32 Fruit Street,
Boston, MA 02114. Phone: (617) 726-7411. Fax: (617) 726-3673. E-mail: podolsky.daniel{at}mgh.harvard.edu.
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