Specialized pro-resolving mediator (SPM) biosynthesis (SPM biosynthesis)

Specialized pro-resolving mediator (SPM) biosynthesis is the enzymatic process responsible for producing lipid signaling molecules—such as lipoxins, resolvins, protectins, and maresins—that actively coordinate the resolution phase of inflammation (Serhan & Levy, 2018). Unlike traditional anti-inflammatory drugs that inhibit the onset of inflammation, targeting SPM biosynthesis aims to promote the 'switch' from pro-inflammatory to pro-resolving signals, facilitating the clearance of debris and the restoration of tissue homeostasis (Chiang & Serhan, 2020). This pathway involves key enzymes including lipoxygenases (5-LOX, 12-LOX, 15-LOX) and cyclooxygenase-2 (COX-2), which metabolize polyunsaturated fatty acids like arachidonic acid, EPA, and DHA (Dalli et al., 2013). Dysregulation of SPM biosynthesis is linked to chronic inflammatory conditions, including asthma, rheumatoid arthritis, and cardiovascular disease (Basil & Levy, 2016). Therapeutic strategies include the use of aspirin to trigger 'aspirin-triggered' SPMs or the development of stable SPM mimetics to treat unresolved inflammatory states (Serhan, 2014). Overall, modulating SPM biosynthesis represents a novel paradigm in pharmacology focused on resolution rather than simple inhibition.

Other names

SPM pathwayResolution of inflammation pathwayPro-resolving lipid mediator synthesisLipid mediator class switching

Promotion of the enzymatic conversion of polyunsaturated fatty acids into pro-resolving lipid mediators, or the use of aspirin to acetylate COX-2, shifting its activity toward the production of 15R-HETE and subsequent aspirin-triggered resolvins and lipoxins (Serhan, 2014).