Omega-3 fatty acids and docosahexaenoic acid oxymetabolites modulate the inflammatory response of equine recombinant interleukin1β-stimulated equine synoviocytes.
Abstract: Omega-3 fatty acid (n-3 PUFA) supplementation may have beneficial effects in certain chronic diseases, potentially including osteoarthritis. Favorable effects are attributed, in part, to downstream pro-resolving oxylipid metabolites. We investigated the role of n-3 PUFA and docosahexaenoic acid (DHA)-derived oxylipids (docosanoids) on equine synoviocyte metabolism. We hypothesized that n-3 PUFA and selected docosanoids would modulate inflammatory mediator gene expression by recombinant equine (re)IL-1β-stimulated synovial fibroblasts. Synoviocyte monolayer cultures were prepared from grossly normal equine carpal synovium. Cellular incorporation of eicosapentaenoic acid (EPA) and DHA was determined using LC-MS and docosanoid biosynthesis by LC-MS-MS. The influence of n-3 PUFA and docosanoids on osteoarthritis marker gene expression was determined by quantitative real time polymerase chain reaction (qPCR). Synoviocytes incorporated EPA and DHA in significant amounts and DHA treatment augmented the synthesis of several docosanoids. Synoviocyte cultures pre-treated with EPA or DHA followed by reIL-1β stimulation had significant reductions in expression of ADAMTS4, MMP-1, MMP-13, IL-1β, IL-6 and COX-2. The docosanoids resolvin D1 and D2, maresin 1 and protectin DX, alone and in combination, abrogated ADAMTS4, MMP-1, MMP-13, and IL-6 gene expression in reIL-1β-stimulated synoviocytes. Similarly, both resolvins and maresin 1 stifled COX-2 expression. Our results demonstrate that synoviocytes readily incorporate n-3 PUFA. DHA incorporation was sufficient for biosynthesis of significant concentrations of several docosanoids which modulated the synovial inflammatory response in vitro. These data indicate n-3 PUFA supplementation may prove useful in the prevention or treatment of osteoarthritis.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication Date: 2019-03-02 PubMed ID: 30836143DOI: 10.1016/j.prostaglandins.2019.02.007Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates the effects of Omega-3 fatty acids and certain derivatives on the inflammation in joint cells of horses. The results suggest that these compounds may have a potential role in preventing or treating osteoarthritis.
Objective of the Study
- The study aimed to explore the role of Omega-3 fatty acids and docosahexaenoic acid (DHA)-derived oxylipids (docosanoids) on the metabolism of synoviocytes, the cells that line the inner part of joint cavities.
- It was hypothesized that these compounds would influence the gene expression of inflammatory mediators in interleukin1β-stimulated synoviocytes, thus potentially indicating their effect on osteoarthritis, a chronic disease characterized by joint inflammation.
Methodology and Results
- Synoviocyte monolayer cultures were created using equine carpal synovium, a tissue found within equine joints.
- The incorporation of eicosapentaenoic acid (EPA) and DHA into cells was determined using liquid chromatography–mass spectrometry (LC-MS) and the synthesis of docosanoids was examined using liquid chromatography–tandem mass spectrometry (LC-MS-MS).
- It was determined that treatment with DHA increased the synthesis of several types of docosanoids.
- Molecular analysis using quantitative real-time polymerase chain reaction (qPCR) indicated that pre-treatment with EPA or DHA caused a significant reduction in the expression of key inflammatory mediators (ADAMTS4, MMP-1, MMP-13, IL-1β, IL-6 and COX-2).
- Furthermore, the docosanoids resolvin D1 and D2, maresin 1 and protectin DX single or combined also effectively reduced the gene expression of these inflammatory mediators in IL-1β-stimulated synoviocytes.
- It was also found that n-3 PUFA were efficiently incorporated into synoviocytes, suggesting that cells could readily uptake these compounds.
Conclusion and Implications
- The results of the study indicate that Omega-3 fatty acids and the DHA-derived docosanoids had a significant dampening effect on the expression of inflammatory mediators in synoviocytes, pointing at their potential anti-inflammatory role in joint health.
- This suggests that supplementation with Omega-3 fatty acids might have potential utility in the prevention or management of osteoarthritis; however, further research is needed in vivo to confirm these in vitro findings.
Cite This Article
APA
Caron JP, Gandy JC, Brown JL, Sordillo LM.
(2019).
Omega-3 fatty acids and docosahexaenoic acid oxymetabolites modulate the inflammatory response of equine recombinant interleukin1β-stimulated equine synoviocytes.
Prostaglandins Other Lipid Mediat, 142, 1-8.
https://doi.org/10.1016/j.prostaglandins.2019.02.007 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48823-1314, United States. Electronic address: caron@cvm.msu.edu.
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48823-1314, United States.
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48823-1314, United States.
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48823-1314, United States.
MeSH Terms
- Animals
- Cytokines / metabolism
- Docosahexaenoic Acids / metabolism
- Docosahexaenoic Acids / pharmacology
- Docosahexaenoic Acids / therapeutic use
- Eicosapentaenoic Acid / metabolism
- Eicosapentaenoic Acid / pharmacology
- Fibroblasts / drug effects
- Fibroblasts / metabolism
- Gene Expression Regulation / drug effects
- Horses
- Inflammation / metabolism
- Inflammation / pathology
- Interleukin-1beta / pharmacology
- Osteoarthritis / drug therapy
- Osteoarthritis / metabolism
- Osteoarthritis / pathology
- Recombinant Proteins / pharmacology
- Synoviocytes / drug effects
- Synoviocytes / metabolism
- Synoviocytes / pathology
Citations
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