| dc.description.abstract | The aim of this project is to investigate how an omega-3 fatty acids diet (n-3) and its lipid mediators could promote resolution of inflammation in arthritis. C57BL/6 mice were administered with K/BxN serum to induce inflammatory arthritis, and fed either with normal, n-3 or western diet. Mice fed with an n-3 diet exhibited reduced arthritic score and paw oedema compared to normal diet. Flow cytometry cell phenotyping of the paws revealed several changes in the n-3 group, such as an increased amount of pro-resolution CD206+MerTK+ macrophages and protective CX3CR1+ macrophages at peak of arthritis. The n-3 diet group also recorded a higher amount of MHC II+ and FPR2+ fibroblasts. Paw lipidomics analyses identified higher levels of EPA-derived RvE2 and RvE4 in n-3 -fed animals. These two specialised pro-resolving lipid mediators (SPM) were injected as daily treatment in mice challenged with inflammatory arthritis. The SPMs-treated group was associated with improved arthritis, as arthritic score, paw oedema and weight loss were less marked in these mice, when compared to saline-treated control. These macroscopic changes were also associated with an increased proportion of CD206+MerTK+ macrophages in the paws at resolution. A combination of RvE2+RvE4 did not show any effect in an experimental model of osteoarthritis (OA), and in vitro studies on C-28/I2 human chondrocytes micromasses and human primary articular chondrocytes gave mixed results, thus the potential effect on OA cartilage is not confirmed. Whole blood from human healthy and arthritic donors was treated with RvE2+RvE4. Cell phenotyping showed that the treatment reduced expression of markers associated with cell migration (such as CD54) and cell activation (such as CD69) in both innate and adaptive immune cells. Taken together, these findings reveal a beneficial effect of n-3 in arthritis, and promising effect of RvE2+RvE4 in a mouse model of inflammatory arthritis and in human whole blood. | en_US |
