Local shifts in inflammatory and resolving lipid mediators in response to tendon overuse.

Autor: Markworth JF; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.; Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA., Sugg KB; Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.; Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Sarver DC; Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.; Department of Cellular & Molecular Physiology, Johns Hopkins University, Baltimore, MD, USA., Maddipati KR; Department of Pathology, Lipidomics Core Facility, Wayne State University, Detroit, MI, USA., Brooks SV; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Jun; Vol. 35 (6), pp. e21655.
DOI: 10.1096/fj.202100078R
Abstrakt: Tendon inflammation has been implicated in both adaptive connective tissue remodeling and overuse-induced tendinopathy. Lipid mediators control both the initiation and resolution of inflammation, but their roles within tendon are largely unknown. Here, we profiled local shifts in intratendinous lipid mediators via liquid chromatography-tandem mass spectrometry in response to synergist ablation-induced plantaris tendon overuse. Sixty-four individual lipid mediators were detected in homogenates of plantaris tendons from ambulatory control rats. This included many bioactive metabolites of the cyclooxygenase (COX), lipoxygenase (LOX), and epoxygenase (CYP) pathways. Synergist ablation induced a robust inflammatory response at day 3 post-surgery characterized by epitenon infiltration of polymorphonuclear leukocytes and monocytes/macrophages (MΦ), heightened expression of inflammation-related genes, and increased intratendinous concentrations of the pro-inflammatory eicosanoids thromboxane B 2 and prostaglandin E 2 . By day 7, MΦ became the predominant myeloid cell type in tendon and there were further delayed increases in other COX metabolites including prostaglandins D 2 , F 2α , and I 2 . Specialized pro-resolving mediators including protectin D1, resolvin D2 and D6, as well as related pathway markers of D-resolvins (17-hydroxy-docosahexaenoic acid), E-resolvins (18-hydroxy-eicosapentaenoic acid), and lipoxins (15-hydroxy-eicosatetraenoic acid) were also increased locally in response to tendon overuse, as were anti-inflammatory fatty acid epoxides of the CYP pathway (eg, epoxy-eicosatrienoic acids). Nevertheless, intratendinous prostaglandins remained markedly increased even following 28 days of tendon overuse together with a lingering MΦ presence. These data reveal a delayed and prolonged local inflammatory response to tendon overuse characterized by an overwhelming predominance of pro-inflammatory eicosanoids and a relative lack of specialized pro-resolving lipid mediators.
(© 2021 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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