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Review
. 2013 Sep;19(10):2238-44.
doi: 10.1097/MIB.0b013e31828dcaaf.

The inflammatory tissue microenvironment in IBD

Sean P Colgan  1 , Valerie F Curtis, Eric L Campbell
Affiliations
Review

The inflammatory tissue microenvironment in IBD

Sean P Colgan et al. Inflamm Bowel Dis. 2013 Sep.

Abstract

A current view of the inflammatory bowel diseases (IBDs) includes the luminal triggering of innate immune disease in a genetically susceptible host. Given the unique anatomy and complex environment of the intestine, local microenvironmental cues likely contribute significantly to both disease progression and resolution in IBD. Compartmentalized tissue and microbe populations within the intestine result in significant metabolic shifts within these tissue microenvironments. During active inflammatory disease, metabolic demands often exceed supply, resulting in localized areas of metabolic stress and diminished oxygen delivery (hypoxia). There is much recent interest in harnessing these microenvironmental changes to the benefit of the tissue, including targeting these pathways for therapy of IBD. Here, we review the current understanding of metabolic microenvironments within the intestine in IBD, with discussion of the advantages and disadvantages of targeting these pathways to treat patients with IBD.

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Conflict of interest statement

Competing interests

The authors declare no competing interests.

Figures

Figure 1
Figure 1. Signaling within the microenvironment of the crypt abscess
Transmigrating PMN become activated to consume large amounts of oxygen in the formation of superoxide anions (termed the PMN oxygen burst). As a result, the localized microenvironment becomes depleted of molecular O2, and culminates in the stabilization of HIF. The activation of multiple HIF target genes (see text) promotes the active resolution of inflammation within the mucosa.
Figure 2
Figure 2. Nucleotide and lipid mediator metabolism as pro-resolving signals generated in the microenvironment
In model A, activated PMN release large amounts of ATP during transmigration. This ATP is subsequently metabolized to adenosine by a two-step enzymatic reaction involving ecto-apyrase (CD39) and ecto-nucleotidase (CD73). Adenosine binding to apical adenosine A2B receptors promotes the resolution of inflammation. In model B, RvE1 production is amplified by transcellular biosynthesis via the interactions of PMN with epithelial cells during transmigration, each contributing an enzymatic product. In the example shown here, epithelial cell COX-2 generates 18-HEPE from dietary omega-3 PUFA and PMN-expressed 5-LO then generates RvE1. Such locally generated RvE1 is then made available to activate apically expressed ChemR23 which in turn promotes resolution through a number of mechanisms (see text).
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