Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4622
Peer-review started: July 5, 2018
First decision: August 25, 2018
Revised: October 8, 2018
Accepted: October 16, 2018
Article in press: October 16, 2018
Published online: November 7, 2018
The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of non-immune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct pro-inflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD. The effects determine pathologic changes, which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes. In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers, research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.
Core tip: Damage-associated molecular patterns (DAMPs) are basically endogenous stress molecules expressed or released as a consequence of cell or tissue damage. The release of endogenous DAMPs precipitates a secondary inflammatory response in inflammatory bowel disease (IBD), which may determine a self-sustaining chronic inflammatory process. DAMPs amplify the inflammatory response driven by immune and non-immune cells and promote several pathologic changes, which may be associated with specific disease phenotypes. Excessive or persistent DAMP-mediated signalling can result in epigenetic modifications, which may sustain chronic inflammation and also characterize IBD phenotypes. Preliminary studies targeting DAMPs have shown promising beneficial therapeutic effects both in human and experimental IBD.