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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2018; 24(41): 4622-4634
Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4622
Damage-associated molecular patterns in inflammatory bowel disease: From biomarkers to therapeutic targets
Hayandra Ferreira Nanini, Claudio Bernardazzi, Fernando Castro, Heitor Siffert Pereira de Souza
Hayandra Ferreira Nanini, Claudio Bernardazzi, Fernando Castro, Heitor Siffert Pereira de Souza, Serviço de Gastroenterologia e Laboratório Multidisciplinar de Pesquisa, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
Heitor Siffert Pereira de Souza, D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, RJ 22281-100, Brazil
Author contributions: Nanini HF, Bernardazzi C, and Castro F participated in the conception of the study, the acquisition, analysis, and interpretation of the literature; and the drafting of the manuscript. de Souza HSP participated in the conception of the study, obtained funding, analysed and interpreted data, and critically revised the manuscript for important intellectual content. All authors gave final approval of the submitted version of the manuscript.
Supported by the Brazilian research foundations Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro-FAPERJ, No. E26/202.781/2017; and Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, No. 302401/2016-4.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding the publication of this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Heitor Siffert Pereira de Souza, MD, PhD, Associate Research Scientist, Full Professor, Serviço de Gastroenterologia and Laboratório Multidisciplinar de Pesquisa, Departamento de Clínica Médica, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Ilha do Fundão, Rio de Janeiro, RJ 21941-913, Brazil. hsouza@hucff.ufrj.br
Telephone: +55-21-39382669 Fax: +55-21-39382669
Received: July 5, 2018
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
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.

Keywords: Damage-associated molecular patterns, Environmental factors, Epigenetics, Inflammatory bowel disease, 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.