Dataset Information

Proresolving Mediators LXB4 and RvE1 Regulate Inflammation in Stromal Cells from Patients with Shoulder Tendon Tears.

ABSTRACT: Tendon stromal cells isolated from patients with chronic shoulder rotator cuff tendon tears have dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation; therefore, new therapeutic approaches that target tendon stromal cells are required. We examined whether two specialized proresolving mediators (SPMs), lipoxin B4 (LXB4) and resolvin E1 (RvE1), modulate the bioactive lipid mediator profiles of IL-1?-stimulated tendon cells derived from patients with shoulder tendon tears and healthy volunteers. We also examined whether LXB4 or RvE1 treatments moderated the proinflammatory phenotype of tendon tear stromal cells. Incubation of IL-1?-treated patient-derived tendon cells in LXB4 or RvE1 up-regulated concentrations of SPMs. RvE1 treatment of diseased tendon stromal cells increased 15-epi-LXB4 and regulated postaglandin F2?. LXB4 or RvE1 also induced expression of the SPM biosynthetic enzymes 12-lipoxygenase and 15-lipoxygenase. RvE1 treatment up-regulated the proresolving receptor human resolvin E1 compared with vehicle-treated cells. Incubation in LXB4 or RvE1 moderated the proinflammatory phenotype of patient-derived tendon tear cells, regulating markers of tendon inflammation, including podoplanin, CD90, phosphorylated signal transducer and activator of transcription 1, and IL-6. LXB4 and RvE1 counterregulate inflammatory processes in tendon stromal cells, supporting the role of these molecules as potential therapeutics to resolve tendon inflammation.

SUBMITTER: Dakin SG

PROVIDER: S-EPMC6876268 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Proresolving Mediators LXB4 and RvE1 Regulate Inflammation in Stromal Cells from Patients with Shoulder Tendon Tears.

Dakin Stephanie G SG Colas Romain A RA Wheway Kim K Watkins Bridget B Appleton Louise L Rees Jonathan J Gwilym Stephen S Little Christopher C Dalli Jesmond J Carr Andrew J AJ

The American journal of pathology 20190819 11

Tendon stromal cells isolated from patients with chronic shoulder rotator cuff tendon tears have dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation; therefore, new therapeutic approaches that target tendon stromal cells are required. We examined whether two specialized proresolving mediators (SPMs), lipoxin B4 (LXB4) and resolvin E1 (RvE1), modulate the bioactive lipid mediator profiles of IL-1β-stimulated te ...[more]

PMID: 31437425

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Project description:Objective To identify transcript level differences between traumatic and degenerative tears of tendon tissues in shoulder joint using RNA-seq. Methods Tendon tissues were isolated from female and male patients with traumatic or degenerative tears during arthroscopic surgery (N = 31). Differentially expressed transcript were identified and biological processes enriched in traumatic and degenerative tears were probed computationally. Expression pattern of selected transcripts was validated by real-time qPCR. Results We identified 339 and 336 transcripts differentially expressed between traumatic and degenerative tears in females and males respectively at a fold-change greater than |2| and a p-value  0.05. In females, GSTM1, MT1G, S1008A, ACSM3, DSC, FAM110C and VNN2 were the most prominent transcripts elevated in traumatic tears and CHAD, CLEC3A, IBSP, TNMD, APLNR, and CPA3 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented catabolic processes, immune response, and metabolic processes while those repressed in traumatic tears represented tissue morphogenesis and developmental processes, angiogenesis, and extracellular matrix organization. In males, ELOA3B, CXCL8, ADM, TNS4 and SPOCK1 were the most prominent transcripts elevated in traumatic tears and MYL2, TNNC1, MB, CPA3, APLNR, and CA3 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented localization of endoplasmic reticulum, chromosome organization, leukocyte/neutrophil degranulation, and protein transport whereas those repressed in traumatic tears represented muscle development, blood circulation (angiogenesis), and muscle cell differentiation. Numerous novel lncRNAs were also identified to be differentially expressed between traumatic and degenerative tears in both sexes. Conclusions and Clinical Relevance This study improves our molecular understanding of tendon tissues in patients with rotator cuff tendinopathy based on underlying etiology (trauma and degeneration). It also provides new insights into sex-based transcript differences that may help drive clinical decision making in female and male patients with traumatic and degenerative shoulder injuries.

Project description:The current crises in opioid abuse and chronic pain call for the development of nonopioid and nonpharmacological therapeutics for pain relief. Neuromodulation-based approaches, such as spinal cord stimulation, dorsal root ganglion simulation, and nerve stimulation including vagus nerve stimulation, have shown efficacy in achieving pain control in preclinical and clinical studies. However, the mechanisms by which neuromodulation alleviates pain are not fully understood. Accumulating evidence suggests that neuromodulation regulates inflammation and neuroinflammation-a localized inflammation in peripheral nerves, dorsal root ganglia/trigeminal ganglia, and spinal cord/brain-through neuro-immune interactions. Specialized proresolving mediators (SPMs) such as resolvins, protectins, maresins, and lipoxins are lipid molecules produced during the resolution phase of inflammation and exhibit multiple beneficial effects in resolving inflammation in various animal models. Recent studies suggest that SPMs inhibit inflammatory pain, postoperative pain, neuropathic pain, and cancer pain in rodent models via immune, glial, and neuronal modulations. It is noteworthy that sham surgery is sufficient to elevate resolvin levels and may serve as a model of resolution. Interestingly, it has been shown that the vagus nerve produces SPMs and vagus nerve stimulation (VNS) induces SPM production in vitro. In this review, we discuss how neuromodulation such as VNS controls pain via immunomodulation and neuro-immune interactions and highlight possible involvement of SPMs. In particular, we demonstrate that VNS via auricular electroacupuncture effectively attenuates chemotherapy-induced neuropathic pain. Furthermore, auricular stimulation is able to increase resolvin levels in mice. Thus, we propose that neuromodulation may control pain and inflammation/neuroinflammatioin via SPMs. Finally, we discuss key questions that remain unanswered in our understanding of how neuromodulation-based therapies provide short-term and long-term pain relief.

Dataset Information

Proresolving Mediators LXB4 and RvE1 Regulate Inflammation in Stromal Cells from Patients with Shoulder Tendon Tears.

Publications

Proresolving Mediators LXB4 and RvE1 Regulate Inflammation in Stromal Cells from Patients with Shoulder Tendon Tears.

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