Damage-Associated Molecular Patterns in Inflammatory Diseases

Jong Seong Roh; Dong Hyun Sohn

doi:10.4110/in.2018.18.e27

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Roh and Sohn: Damage-Associated Molecular Patterns in Inflammatory Diseases

Review Article

Immune Netw 2018;18(4):e27.

Published online: 4 August 2018

DOI: https://doi.org/10.4110/in.2018.18.e27

Damage-Associated Molecular Patterns in Inflammatory Diseases

Jong Seong Roh, Dong Hyun Sohn^*

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

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

Conflict of Interest The authors declare no potential conflicts of interest.

Received 2 June 2018 Revised 5 August 2018 Accepted 5 August 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://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.

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.

Keywords: Damage-associated molecular patterns, Inflammation, Pattern recognition receptors, Inflammatory diseases

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Figure 1.

DAMPs as biomarkers and potential therapeutic targets. DAMPs are released upon cellular stress or tissue injury and activate the innate immune system by interacting with PRRs to produce proinflammatory cytokines. Chronic inflammation can contribute to the development of various inflammatory diseases, which in turn stimulate the secretion of DAMPs, thus establishing a vicious cycle of DAMPs production and inflammation.

Table 1.

List of DAMPs and their receptors

Origin		Major DAMPs	Receptors
Extracellular matrix		Biglycan	TLR2, TLR4, NLRP3
		Decorin	TLR2, TLR4
		Versican	TLR2, TLR6, CD14
		LMW hyaluronan	TLR2, TLR4, NLRP3
		Heparan sulfate	TLR4
		Fibronectin (EDA domain)	TLR4
		Fibrinogen	TLR4
		Tenascin C	TLR4
Intracellular compartments	Cytosol	Uric acid	NLRP3, P2X7
		S100 proteins	TLR2, TLR4, RAGE
		Heat shock proteins	TLR2, TLR4, CD91
		ATP	P2X7, P2Y2
		F-actin	DNGR-1
		Cyclophilin A	CD147
	Nuclear	Aβ Histones	TLR2, TLR4 TLR2, NLRP1, NLRP3, CD36, RAGE
		HMGB1	TLR2, TLR4, RAGE
		HMGN1	TLR4
		IL-1α IL-33	IL-1R ST2
		SAP130	Mincle
		DNA	TLR9, AIM2
		RNA	TLR3, TLR7, TLR8, RIG-I, MDA5
	Mitochondria	mtDNA	TLR9
		TFAM	RAGE
		Formyl peptide	FPR1
		mROS	NLRP3
	ER	Calreticulin	CD91
	Granule	Defensins	TLR4
		Cathelicidin (LL37)	P2X7, FPR2
		EDN	TLR2
		Granulysin	TLR4
	Plasma membrane	Syndecans	TLR4
		Glypicans	TLR4

ER, endoplasmic reticulum; EDN, eosinophil-derived neurotoxin.

Table 2.

PRRs and their DAMP ligands

Family	Major members	DAMP ligands
TLRs	TLR1–9	HMGB1, HSPs, S100 proteins, histones, DNA, RNA, mtDNA, syndecans, glypicans, biglycan, decorin, versican, LMW hyaluronan, heparan sulfate, fibrinogen, tenascin C
NLRs	NOD1, NOD2, NLRP family	Uric acid, Aβ, mROS, histones, biglycan, LMW hyaluronan
RLRs	RIG-I, MDA5, LGP2	RNA
CLRs	DEC-205, MMR, Dectin-1, Dectin-2, Mincle, DC-SIGN, DNGR-1	SAP130, F-actin
CDSs	AIM2-like receptor	DNA
Scavenger receptors	CD36, CD44, CD68, CD91, CXCL16, RAGE	HMGB1, HSPs, S100 proteins, calreticulin, versican
FPRs	FPR1, FPR2, FPR3	Formyl peptide, cathelicidin (LL37)

NLR, NOD-like receptor; CLR, C-type lectin receptor; CDS, cytosolic DNA sensor; FPR, formyl peptide receptor; LMW, low molecular weight.

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