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

• DOI: 10.1172/jci.insight.85922
• Publication Date: 2016-04-20T15:01:01Z
• Authors: Lucy V. Norling; Sarah E. Headland; Jesmond Dalli; Hildur H. Arnardo...; Oliver Haworth; Hefin R. Jones; Daniel Irimia; Charles N. Serhan; Mauro Perretti
• Keywords: Docosahexaenoic Acids; Arthritis; 616; R; 610; Medicine; Humans; Corrigendum; Research Article; 3. Good health

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