New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPA...

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Main Authors: Miriam D. Neher, Sebastian Weckbach, Markus S. Huber-Lang, Philip F. Stahel
Format: Article
Language:English
Published: Hindawi Limited 2012-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2012/728461
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spelling doaj-db1e3ecf50fc45b09e5dab159b188efd2020-11-24T22:39:29ZengHindawi LimitedPPAR Research1687-47571687-47652012-01-01201210.1155/2012/728461728461New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue InjuryMiriam D. Neher0Sebastian Weckbach1Markus S. Huber-Lang2Philip F. Stahel3Department of Orthopaedic Surgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204, USADepartment of Orthopaedic Surgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204, USADepartment of Trauma and Reconstructive Surgery, University Hospital Ulm, Steinhövelstraße 9, D-89075 Ulm, GermanyDepartment of Orthopaedic Surgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204, USAMajor trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed.http://dx.doi.org/10.1155/2012/728461
collection DOAJ
language English
format Article
sources DOAJ
author Miriam D. Neher
Sebastian Weckbach
Markus S. Huber-Lang
Philip F. Stahel
spellingShingle Miriam D. Neher
Sebastian Weckbach
Markus S. Huber-Lang
Philip F. Stahel
New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
PPAR Research
author_facet Miriam D. Neher
Sebastian Weckbach
Markus S. Huber-Lang
Philip F. Stahel
author_sort Miriam D. Neher
title New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
title_short New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
title_full New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
title_fullStr New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
title_full_unstemmed New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
title_sort new insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury
publisher Hindawi Limited
series PPAR Research
issn 1687-4757
1687-4765
publishDate 2012-01-01
description Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed.
url http://dx.doi.org/10.1155/2012/728461
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