Specialized pro-resolving mediators biosynthetic pathway (SPM biosynthetic pathway)

The specialized pro-resolving mediators (SPM) biosynthetic pathway is a complex enzymatic network that governs the active resolution phase of inflammation [4, 5]. It facilitates the conversion of essential polyunsaturated fatty acids (PUFAs)—such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)—into potent bioactive autacoids including lipoxins, resolvins, protectins, and maresins [1, 7]. This process involves a sequential action of enzymes, primarily 5-lipoxygenase (ALOX5), 12-lipoxygenase (ALOX12), 15-lipoxygenase (ALOX15), and cyclooxygenase-2 (COX-2) [2, 8]. The biological role of these mediators is to curtail further neutrophil recruitment, stimulate the non-phlogistic clearance of apoptotic cells and microbes by macrophages (efferocytosis), and initiate tissue regeneration [1, 4]. Dysregulation or a "resolution deficit" in this pathway is linked to the development of chronic inflammatory diseases, including cardiovascular disease, neurodegeneration, and metabolic disorders [7, 9]. Pharmacological modulation of the pathway is a key focus of resolution pharmacology; for example, low-dose aspirin can acetylate COX-2 to shift its activity toward the production of "aspirin-triggered" (AT) epimers of resolvins and lipoxins [5, 9]. Furthermore, nutritional supplementation with omega-3 fatty acids provides the necessary substrates to maintain high levels of these pro-resolving mediators [2, 3].

Other names

Pro-resolution pathwayLipid mediator class-switching pathwaySpecialized pro-resolving mediator pathwayResolution of inflammation pathwaySPM biosynthesis

Enhancement of pro-resolving lipid mediator synthesis through the provision of essential fatty acid substrates or the allosteric modulation of biosynthetic enzymes to shift metabolic flux from pro-inflammatory to pro-resolving pathways.