D-series resolvin biosynthetic pathway

The D-series resolvin biosynthetic pathway refers to the enzymatic cascade producing specialized pro-resolving mediators (SPMs) derived from docosahexaenoic acid (DHA), including resolvin D1 (RvD1; 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid), resolvin D2 (RvD2; 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), and resolvin conjugate in tissue regeneration-1 (RCTR1). It initiates with 15-lipoxygenase (15-LOX) forming 17S-hydroperoxy-DHA, followed by 5-lipoxygenase (5-LOX) generating a transient 7,8(S,S)-epoxytetraene intermediate, which is then converted by epoxide hydrolases like soluble epoxide hydrolase (sEH) or glutathione S-transferase LTC4 synthase (LTC4S) into the final trihydroxy products via stereospecific hydrolysis or conjugation in immune cells such as neutrophils, macrophages, and keratinocytes. These resolvins actively promote inflammation resolution by enhancing clearance of debris, apoptotic cells, and pathogens, while stimulating tissue repair processes like epidermal re-epithelialization and keratinocyte migration through receptors such as ALX/FPR2 and DRV2, activating pathways including PI3K-AKT-mTOR-S6. In disease contexts, dysregulation of this pathway contributes to chronic inflammation and impaired wound healing, with topical or endogenous resolvins showing therapeutic potential in expediting skin injury resolution and reducing hyperalgesia in arthritis models, though it is not a direct druggable target like a receptor or enzyme but rather a multi-step cellular process.

Other names

D-series resolvin synthesis pathwayRvD biosynthetic pathwaybiosynthesis of resolvins D1, D2, and related mediators