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

Abstract

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.

Temporal expression profiling of DAMPs-related genes revealed the biphasic post-ischemic inflammation in the experimental stroke model

“…DAMPs comprise a quite diverse group of discompartmentalized self-structures and ECM [6,7]. We here classified DAMPs-related genes into several categories depending on the hierarchical cascades, including DAMPs, receptors, downstream cascades, mediators, and phagocytosis as shown in the schematic diagram (Fig.…”

“…DAMPs comprise a quite diverse group of discompartmentalized self-structures and ECM (extracellular matrix) [6,7]. Pattern recognition receptors (PRRs), initially discovered for their role in recognizing PAMPs (pathogen-associated molecular patterns), relate to the sterile inflammation in response to DAMPs.…”

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

“…8,[10][11][12][13][14][15][16][17][18][19][20][21] Based on a series of fundamental studies, preclinical validations and clinical biomarker assessments [22][23][24] ICD can be defined as a functionally unique RCD subtype that is sufficient for the elicitation of adaptive immunity specifically directed toward antigens derived from cell "corpses". 4, 9,12,15,21,[25][26][27][28][29][30][31][32][33][34][35][36] It is now well acknowledged that, upon antigenic priming coupled to the emission of damage-associated molecular patterns (DAMPs) and immunostimulatory cytokines, 8,9,12,15,[19][20][21][27][28][29]31,[36][37][38][39][40]…”

Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors

“…Crohn’s disease (CD) and ulcerative colitis (UC), the most commonly diagnosed types of inflammatory bowel diseases (IBD), are complex, immunologically mediated diseases of the gastrointestinal tract. Despite the differences between CD and UC pathology several phenomena such as dysregulation of the immune response, the gut microbiome, as well as genetic and environmental factors seem to be crucial in IBD pathogenesis [1,2,3]. Males are more likely to develop UC, whereas females are more likely to develop CD [4,5].…”