Potential of specialized pro-resolving lipid mediators against rheumatic diseases.
While arachidonic acid (AA), which is classified into n-6 polyunsaturated fatty acid (PUFA), has been mainly recognized as a substrate of pro-inflammatory mediators, eicosapentaenoic acid or docosahexaenoic acid, which are classified into n-3 PUFA, is currently identified as substrates of mediators inducing resolution of inflammation, namely pro-resolving mediators (SPM). As with any other pathological conditions, it is gradually elucidated that SPMs contributes a certain effect on joint inflammation. In osteoarthritis (OA), Lipid fractions extracted from adipocytes, especially in infrapatellar fat pad rather than subcutaneous tissue induce T cell skewing for producing IFN-γ or decrease the production of IL-12p40 from macrophages. In synovial tissues form OA, there are some of known receptors for SPM. In the synovial fluid from rheumatoid arthritis (RA), it could be identified and quantified a certain kind of SPMs such as maresin 1, lipoxin A4 and resolvin D5. In murine models of arthritis, some of SPMs are found to have some functions to reduce tissue damage. Correctively, SPMs might have some potential to a novel therapeutic target for arthritis or any other rheumatic diseases.
Department of Rheumatology and Clinical Immunology, Kyoto University Hospital.
Kosaku
K
Murakami
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000502:physiology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000502:physiology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects; D006801:Humans; D018836:Inflammation Mediators / Q000009:adverse effects; D007371:Interferon-gamma / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D058990:Molecular Targeted Therapy; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D013582:Synovial Fluid / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D007371:Interferon-gamma; D015118:Eicosapentaenoic Acid