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

Stephanie G Dakin1, Romain A Colas2, Kim Wheway1

  • 1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Nuffield Orthopaedic Centre, Oxford, United Kingdom.

The American Journal of Pathology
|August 23, 2019
PubMed

Insights

Specialized proresolving mediators lipoxin B4 (LXB4) and resolvin E1 (RvE1) can resolve inflammation in shoulder rotator cuff tendon tears. These molecules modulate lipid mediators and reduce inflammatory markers in patient-derived tendon cells.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Cell Biology

Background:

  • Tendon stromal cells from chronic rotator cuff tears exhibit impaired inflammation resolution.
  • Current therapies lack efficacy in addressing persistent tendon inflammation.
  • Novel therapeutic strategies targeting tendon stromal cells are needed.

Purpose of the Study:

  • To investigate the effects of lipoxin B4 (LXB4) and resolvin E1 (RvE1) on bioactive lipid mediator profiles in IL-1β-stimulated tendon cells.
  • To determine if LXB4 or RvE1 can mitigate the pro-inflammatory phenotype of tendon tear stromal cells.

Main Methods:

  • Tendon stromal cells from patients with shoulder tendon tears and healthy volunteers were stimulated with IL-1β.
  • Cells were treated with LXB4 or RvE1 to assess modulation of lipid mediators and inflammatory markers.
  • Analysis included quantification of specialized proresolving mediators (SPMs), SPM biosynthetic enzymes, and inflammatory gene/protein expression.

Main Results:

  • LXB4 and RvE1 treatments increased SPM concentrations in patient-derived tendon cells.
  • RvE1 upregulated 15-epi-LXB4 and prostaglandin F2α, and induced SPM biosynthetic enzymes (12-lipoxygenase and 15-lipoxygenase).
  • LXB4 and RvE1 moderated the pro-inflammatory phenotype by regulating markers such as podoplanin, CD90, phosphorylated signal transducer and activator of transcription 1, and IL-6.

Conclusions:

  • LXB4 and RvE1 effectively counterregulate inflammatory processes in tendon stromal cells.
  • These findings support the potential of LXB4 and RvE1 as therapeutic agents for resolving tendon inflammation.
  • Targeting tendon stromal cells with SPMs offers a promising approach for treating chronic rotator cuff tears.

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