Therapeutic applicability of anti-inflammatory and proresolving polyunsaturated fatty acid-derived lipid mediators.
The enzymatic oxygenation of polyunsaturated fatty acids by lipoxygenases and cyclo-oxygenases is a resourceful mode of formation of specific autacoids that regulate the extent and pace of the inflammatory response. Arachidonate-derived eicosanoids, such as lipoxin A4, prostaglandin (PG)D2, PGF2alpha, PGE2, and PGD2-derived cyclopentenones exert specific roles in counter-regulating inflammation and turning on resolution. Recently recognized classes of autacoids derived from long-chain ?-3 polyunsaturated fatty acids, the E- and D-series resolvins, protectin D1, and maresin 1, act as specialized mediators to dampen inflammation actively, afford tissue protection, stimulate host defense, and activate resolution. It is held that counter-regulatory lipid mediators and the specific molecular pathways activated by such endogenous agonists may be suitable for pharmacological use in the treatment of inflammatory disease. The anti-inflammatory drug aspirin is a striking example of a drug that is able to act in such a manner, namely through triggering the formation of 15-epi-lipoxin A4 and aspirin-triggered resolvins. Different aspects of the therapeutic applicability of lipid mediators have been addressed here, and indicate that the development of innovative pharmacotherapy based on anti-inflammatory and proresolution lipid mediators presents novel prospects for the treatment of inflammatory disease.
Bannenberg
Gerard L
GL
Centro Nacional de Biotecnología/CSIC, Department of Plant Molecular Genetics, Campus de la Universidad Autónoma, Madrid. gbannenberg@cnb.csic.es
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism
D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D018836:Inflammation Mediators