Damage-associated molecular patterns in inflammatory bowel disease: From biomarkers to therapeutic targets

• Published in: World journal of gastroenterology : WJG Vol. 24; no. 41; pp. 4622 - 4634
• Main Authors: Nanini, Hayandra Ferreira, Bernardazzi, Claudio, Castro, Fernando, de Souza, Heitor Siffert Pereira
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 07.11.2018
• Subjects: Biomarkers - analysis; Biomarkers - metabolism; Cellular Reprogramming - genetics; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - immunology; Colitis, Ulcerative - microbiology; Colitis, Ulcerative - pathology; Crohn Disease - drug therapy; Crohn Disease - immunology; Crohn Disease - microbiology; Crohn Disease - pathology; Dysbiosis - genetics; Dysbiosis - immunology; Dysbiosis - microbiology; Dysbiosis - pathology; Epigenesis, Genetic; Gastrointestinal Agents - pharmacology; Gastrointestinal Agents - therapeutic use; Gastrointestinal Microbiome - immunology; Genetic Predisposition to Disease; Humans; Inflammation Mediators - analysis; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Leukocyte L1 Antigen Complex - analysis; Leukocyte L1 Antigen Complex - metabolism; Molecular Targeted Therapy - methods; Review; Inflammatory bowel disease; Epigenetics; Environmental factors; Damage-associated molecular patterns; Therapeutic targets
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v24.i41.4622

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.