• Journal article

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Norling, L., Headland, S., Dalli, J., Arnardottir, H., Haworth, O., Jones, H., Irimia, D., Serhan, C. and Perretti, M. 2016. Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis. JCI Insight. 1 (5), p. e85922 e85922. https://doi.org/10.1172/jci.insight.85922

TitleProresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis
TypeJournal article
AuthorsNorling, L., Headland, S., Dalli, J., Arnardottir, H., Haworth, O., Jones, H., Irimia, D., Serhan, C. and Perretti, M.
Abstract

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which - once applied to human neutrophils - attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor-deficient mice termed ALX/fpr2/3-/- . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA.

Keywordsarthritis, resolution, pro-resolving lipid mediators, resolvin D1
Article numbere85922
JournalJCI Insight
Journal citation1 (5), p. e85922
ISSN2379-3708
Year2016
PublisherAmerican Society for Clinical Investigation
Publisher's version
Digital Object Identifier (DOI)https://doi.org/10.1172/jci.insight.85922
Publication dates
Published21 Apr 2016
LicenseCC BY 4.0

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