Open AccessInflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease
Author(s) -
Stephanie G. Dakin,
Jayesh Dudhia,
Natalie Jayne Werling,
Dirk Werling,
D R E Abayasekara,
R. K. W. Smith
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0048978
Subject(s) - lipoxin , inflammation , prostaglandin e , prostaglandin , pathogenesis , lipid signaling , receptor , tendinopathy , tendon , metabolite , endocrinology , eicosanoid , medicine , prostaglandin d2 , cyclooxygenase , chemistry , pathology , biochemistry , arachidonic acid , enzyme
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.