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Innate Immunity and Microbes: Conversations with the Gut Leading to Intestinal Tissue Repair and Fibrosis

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Inflammatory bowel diseases (IBD) are thought to occur because of impaired mucosal integrity that allows enteric bacteria to leak out of the intestine, triggering maladaptive intestinal inflammation. While the exact pathogenesis of IBD is unclear, studies have recently demonstrated that bacterial activation of innate receptors not only causes inflammation, but may also play an important role in modulating intestinal epithelial barrier function, as well as intestinal epithelial cell proliferation and repair. These mucosal homeostatic mechanisms are essential in limiting as well as repairing mucosal damage. Therefore bacterial activation of the innate immune system can have both inflammatory as well as protective healing roles in the intestine. Strikingly, these findings suggest that dysregulation of these processes could be responsible for both the barrier dysfunction as well as the heightened inflammatory tone that characterize IBD. In this review we explore the current state of knowledge underlying this novel role for innate immunity in the gastrointestinal tract, and discuss the strengths and weaknesses of the chemical and infectious models used in these studies. In addition, we discuss preliminary evidence that exaggerated microbial activation of the innate immune system may cause the fibrotic responses that develop in some patients with IBD.

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Keywords: Citrobacter rodentium; IBD; TLR; colitis; dextran sodium sulfate; fibrosis; tissue repair

Document Type: Research Article

Publication date: September 1, 2009

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  • Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Anti-Inflammatory & Anti-Allergy Agents.

    Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Anti-Inflammatory & Anti-Allergy Medicinal Chemistry.

    Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in Anti-Inflammatory & Anti-Allergy Agents drug discovery.
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