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Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease

The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equi...

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Autores principales: Dakin, Stephanie Georgina, Dudhia, Jayesh, Werling, Natalie Jayne, Werling, Dirk, Abayasekara, Dilkush Robert Ephrem, Smith, Roger Kenneth Whealands
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498370/
https://www.ncbi.nlm.nih.gov/pubmed/23155437
http://dx.doi.org/10.1371/journal.pone.0048978
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author Dakin, Stephanie Georgina
Dudhia, Jayesh
Werling, Natalie Jayne
Werling, Dirk
Abayasekara, Dilkush Robert Ephrem
Smith, Roger Kenneth Whealands
author_facet Dakin, Stephanie Georgina
Dudhia, Jayesh
Werling, Natalie Jayne
Werling, Dirk
Abayasekara, Dilkush Robert Ephrem
Smith, Roger Kenneth Whealands
author_sort Dakin, Stephanie Georgina
collection PubMed
description The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E(2) (PGE(2)), F(2α) (PGF(2α)), lipoxin A(4) (LXA(4)) and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE(2) metabolism, microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase (PGDH), COX-2 and EP(4) receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants. Alterations in the profile of lipid mediators during sub-acute injury included low PGE(2) and elevated LXA(4) levels compared to normal and chronic injuries. In contrast, PGF(2α) levels remained unchanged and were three-fold lower than PGE(2). The synthetic capacity of PGE(2) as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP(4) receptor were unchanged. Paradoxically low tendon PGE(2) levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE(2) is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA(4) levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE(2) levels in injury. Furthermore, uninjured tendon explants from younger (<10 years) but not older horses (≥10 years) treated with IL-1β responded by increasing FPR2/ALX suggesting aged individuals exhibit a reduced capacity to resolve inflammation via FPR2/ALX, which may present a potential mechanism for development of chronic tendinopathy and re-injury.
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spelling pubmed-34983702012-11-15 Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease Dakin, Stephanie Georgina Dudhia, Jayesh Werling, Natalie Jayne Werling, Dirk Abayasekara, Dilkush Robert Ephrem Smith, Roger Kenneth Whealands PLoS One Research Article The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E(2) (PGE(2)), F(2α) (PGF(2α)), lipoxin A(4) (LXA(4)) and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE(2) metabolism, microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase (PGDH), COX-2 and EP(4) receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants. Alterations in the profile of lipid mediators during sub-acute injury included low PGE(2) and elevated LXA(4) levels compared to normal and chronic injuries. In contrast, PGF(2α) levels remained unchanged and were three-fold lower than PGE(2). The synthetic capacity of PGE(2) as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP(4) receptor were unchanged. Paradoxically low tendon PGE(2) levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE(2) is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA(4) levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE(2) levels in injury. Furthermore, uninjured tendon explants from younger (<10 years) but not older horses (≥10 years) treated with IL-1β responded by increasing FPR2/ALX suggesting aged individuals exhibit a reduced capacity to resolve inflammation via FPR2/ALX, which may present a potential mechanism for development of chronic tendinopathy and re-injury. Public Library of Science 2012-11-14 /pmc/articles/PMC3498370/ /pubmed/23155437 http://dx.doi.org/10.1371/journal.pone.0048978 Text en © 2012 Dakin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dakin, Stephanie Georgina
Dudhia, Jayesh
Werling, Natalie Jayne
Werling, Dirk
Abayasekara, Dilkush Robert Ephrem
Smith, Roger Kenneth Whealands
Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
title Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
title_full Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
title_fullStr Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
title_full_unstemmed Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
title_short Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
title_sort inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498370/
https://www.ncbi.nlm.nih.gov/pubmed/23155437
http://dx.doi.org/10.1371/journal.pone.0048978
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