The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation.

Abstract:

:Emerging evidence suggests that the innate immune system, comprised of Toll-like receptors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflammation and in the response to invading pathogens. Although TLRs are thought to have predominantly beneficial effects in pathogen recognition and bacterial clearance by leukocytes, their dysregulation and unique signaling effects within intestinal epithelia in the setting of inflammation may have devastating consequences. For instance, activation of TLR4 in enterocytes leads to an inhibition of enterocyte migration and proliferation as well as the induction of enterocyte apoptosis-factors that would be expected to promote intestinal injury while inhibiting intestinal repair. TLR signaling has been shown to be abnormal in several intestinal inflammatory diseases, including Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. This review serves to examine the evidence regarding the patterns of expression and signaling of TLRs in the intestinal mucosa at basal levels and during physiologic stressors to gain insights into the pathogenesis of intestinal inflammation. We conclude that the data reviewed suggest that epithelial TLR signaling-acting in concert with TLR signaling by leukocytes-participates in the development of intestinal inflammation. We further conclude that the evidence reviewed provides a rationale for the development of novel, epithelial-specific, TLR-based agents in the management of diseases of intestinal inflammation.

journal_name

J Leukoc Biol

authors

Gribar SC,Anand RJ,Sodhi CP,Hackam DJ

doi

10.1189/jlb.0607358

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

493-8

issue

3

eissn

0741-5400

issn

1938-3673

pii

jlb.0607358

journal_volume

83

pub_type

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