Key Role of DAMP in Inflammation, Cancer, and Tissue Repair

This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-kno...

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Published in	Clinical therapeutics Vol. 38; no. 5; pp. 1017 - 1028
Main Authors	Pandolfi, Franco, Altamura, Simona, Frosali, Simona, Conti, Pio
Format	Journal Article
Language	English
Published	United States Elsevier Inc 01.05.2016
Subjects	adenosine triphosphate Alarmins Animals ATP cancer damage pattern DAMP high-mobility group box 1 HMGB1 Humans immunology Inflammation Internal Medicine Medical Education Mice Neoplasms Wound Healing damage pattern high-mobility group box 1 inflammation adenosine triphosphate cancer HMGB1 ATP immunology DAMP
Online Access	Get full text
ISSN	0149-2918 1879-114X
DOI	10.1016/j.clinthera.2016.02.028

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Abstract	This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice.
AbstractList	This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice. PURPOSEThis review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively.METHODSWe conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor).FINDINGSA cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury.IMPLICATIONSDue to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice. Abstract Purpose This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. Methods We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). Findings A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Implications Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice.
Author	Frosali, Simona Conti, Pio Altamura, Simona Pandolfi, Franco
Author_xml	– sequence: 1 givenname: Franco surname: Pandolfi fullname: Pandolfi, Franco email: franco.pandolfi@unicatt.it organization: Department of Internal Medicine, School of Medicine, Catholic University, Rome, Italy – sequence: 2 givenname: Simona surname: Altamura fullname: Altamura, Simona organization: Department of Internal Medicine, School of Medicine, Catholic University, Rome, Italy – sequence: 3 givenname: Simona surname: Frosali fullname: Frosali, Simona organization: Department of Internal Medicine, School of Medicine, Catholic University, Rome, Italy – sequence: 4 givenname: Pio surname: Conti fullname: Conti, Pio organization: Postgraduate Medical School, Chieti University, Chieti, Italy
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Snippet	This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of... Abstract Purpose This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the... PURPOSEThis review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role...
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SubjectTerms	adenosine triphosphate Alarmins Animals ATP cancer damage pattern DAMP high-mobility group box 1 HMGB1 Humans immunology Inflammation Internal Medicine Medical Education Mice Neoplasms Wound Healing
Title	Key Role of DAMP in Inflammation, Cancer, and Tissue Repair
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