Toll-Like Receptors as Drug Targets in the Intestinal Epithelium

Abstract

Toll-like receptors (TLRs) receptors are responsible for initiation of inflammatory responses by their recognition of molecular patterns present in invading microorganisms (such as bacteria, viruses or fungi) or in molecules released following tissue damage in disease states. Expressed in the intestinal epithelium, they initiate an intracellular signalling cascade in response to molecular patterns resulting in the activation of transcription factors and the release of cytokines, chemokines and vasoactive molecules. Intestinal epithelial cells are exposed to microorganisms on a daily basis and form part of the primary defence against pathogens by using TLRs. TLRs and their accessory molecules are subject to tight regulation in these cells so as to not overreact or react in unnecessary circumstances. TLRs have more recently been associated with chronic inflammatory diseases as a result of inappropriate regulation, this can be damaging and lead to chronic inflammatory diseases such as inflammatory bowel disease (IBD). Targeting Toll-like receptors offers a potential therapeutic approach for IBD. In this review, the current knowledge on the TLRs is reviewed along with their association with intestinal diseases. Finally, compounds that target TLRs in animal models of IBD, clinic trials and their future merit as targets are discussed.

Keywords: Anti-inflammatory drugs; Inflammatory bowel disease; Intestinal epithelium; Toll-like receptors.