Damage-Associated Molecular Patterns in Inflammatory Diseases

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). Although DAMPs contribute to the host's defense, they promote pathological inflammatory responses. Recent studies have suggested that various DAMPs, such as high-mobility group box 1 (HMGB1), S100 proteins, and heat shock proteins (HSPs), are increased and considered to have a pathogenic role in inflammatory diseases. Here, we review current research on the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. We also discuss the possibility of DAMPs as biomarkers and therapeutic targets for these diseases.

Related collections

Most cited references 56

Record: found
Abstract: found
Article: not found

Signalling through C-type lectin receptors: shaping immune responses

Teunis B H Geijtenbeek, Sonja Gringhuis (2009)

Key Points Crosstalk between pattern recognition receptors (PRRs) expressed by dendritic cells orchestrates T helper (TH) cell differentiation through the induction of specific cytokine expression profiles, tailored to invading pathogens. C-type lectin receptors (CLRs) have an important role in orchestrating the induction of signalling pathways that regulate adaptive immune responses. CLRs can control adaptive immunity at various levels by inducing signalling on their own, through crosstalk with other PRRs or by inducing carbohydrate-specific signalling pathways. DC-specific ICAM3-grabbing non-integrin (DC-SIGN) interacts with mannose-carrying pathogens including Mycobacterium tuberculosis, HIV-1, measles virus and Candida albicans to activate the serine/threonine protein kinase RAF1. RAF1 signalling leads to the acetylation of Toll-like receptor (TLR)-activated nuclear factor-κB (NF-κB) subunit p65 and affects cytokine expression, such as inducing the upregulation of interleukin-10 (IL-10). DC-associated C-type lectin 1 (dectin 1) triggering by a broad range of fungal pathogens, such as C. albicans, Aspergillus fumigatus and Pneumocystis carinii, results in protective antifungal immunity through the crosstalk of two independent signalling pathways — one through spleen tyrosine kinase (SYK) and one through RAF1 — that are essential for the expression of TH1 and TH17 cell polarizing cytokines. Crosstalk between the SYK and RAF1 pathways is both synergistic and antagonizing to fine-tune NF-κB activity: although Ser276 phosphorylation of p65 leads to enhanced transcriptional activity of p65 itself through acetylation, it also inhibits the transcriptional activity of the NF-κB subunit RELB by sequestering it in p65–RELB dimers, which are transcriptionally inactive. The diversity in CLR-mediated signalling provides some major challenges for the researches to elucidate and manipulate the signalling properties of this exciting family of receptors. However, the recent advances strongly support the use of CLR targeting vaccination strategies using dendritic cells to induce or redirect adaptive immune responses as well as improve antigen delivery.

0 comments Cited 396 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

The pathogenesis of rheumatoid arthritis.

Iain B McInnes, Georg Schett (2012)

0 comments Cited 323 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Macrophage activation by endogenous danger signals.

D Mosser, X.-C. Zhang (2007)

Macrophages are cells that function as a first line of defence against invading microorganisms. One of the hallmarks of macrophages is their ability to become activated in response to exogenous 'danger signals'. Most microbes have molecular patterns (PAMPS) that are recognized by macrophages and trigger this activation response. There are many aspects of the activation response to PAMPS that are recapitulated when macrophages encounter endogenous danger signals. In response to damaged or stressed self, macrophages undergo physiological changes that include the initiation of signal transduction cascades from germline-encoded receptors, resulting in the elaboration of chemokines, cytokines and toxic mediators. This response to endogenous mediators can enhance inflammation, and thereby contribute to autoimmune pathologies. Often the overall inflammatory response is the result of cooperative activation signals from both exogenous and endogenous signals. Macrophage activation plays a critical role, not only in the initiation of the inflammatory response but also in the resolution of this response. The clearance of granulocytes and the elaboration of anti-inflammatory mediators by macrophages contribute to the dissolution of the inflammatory response. Thus, macrophages are a key player in the initiation, propagation and resolution of inflammation. This review summarizes our understanding of the role of macrophages in inflammation. We pay particular attention to the endogenous danger signals that macrophages may encounter and the responses that these signals induce. The molecular mechanisms responsible for these responses and the diseases that result from inappropriately controlled macrophage activation are also examined. 2007 Pathological Society of Great Britain and Ireland

0 comments Cited 157 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Immune Netw

Journal ID (iso-abbrev): Immune Netw

Journal ID (publisher-id): IN

Title: Immune Network

Publisher: The Korean Association of Immunologists

ISSN (Print): 1598-2629

ISSN (Electronic): 2092-6685

Publication date Collection: August 2018

Publication date (Electronic): 13 August 2018

Volume: 18

Issue: 4

Electronic Location Identifier: e27

Affiliations

Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan 50612, Korea.

Author notes

Correspondence to Dong Hyun Sohn. Department of Microbiology and Immunology, Pusan National University School of Medicine, 49 Busandaehak-ro, Mulgeum-eup, Yangsan 50612, Korea. dhsohn@ 123456pusan.ac.kr

Article

DOI: 10.4110/in.2018.18.e27

PMC ID: 6117512

PubMed ID: 30181915

SO-VID: 261e41c8-5c72-4c08-81be-4af7c17aa77c

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 02 June 2018

Date revision received : 05 August 2018

Date accepted : 05 August 2018

Funding

Funded by: Pusan National University, CrossRef http://dx.doi.org/10.13039/501100002543;

Damage-Associated Molecular Patterns in Inflammatory Diseases

Read this article at

Abstract

Related collections

HLA-G and immune tolerance in pregnancy

Most cited references 56

Signalling through C-type lectin receptors: shaping immune responses

The pathogenesis of rheumatoid arthritis.

Macrophage activation by endogenous danger signals.

Author and article information

Journal

Affiliations

Author notes

Article

History

Funding

Categories

Comments

Comment on this article

Similar content 457

Cited by 368

Most referenced authors 2,170