32) Resolvins and Protectins in Inflammation-Resolution

Serhan and Petasis; Chem Rev. 2011 October 12; 111(10): 5922–5943

Docosahexaenoic acid (DHA) generally leads to the formation of anti-inflammatory, pro-resolving and cytoprotective lipid mediators
Omega-3 fatty acids EPA and DHA, which are abundant in fish and are widely used as dietary supplements. These essential fatty acids have long been associated with beneficial effects in human health and in the prevention of various diseases, including inflammation, immunomodulation,85 autoimmune diseases, rheumatoid arthritis, Cardiovascular diseases, Alzheimer’s disease and other neurodegenerative diseases,Type-2 diabetes and cancer.

Docosahexaenoic acid (DHA), is the second major component of fish oil and omega-3 nutritional supplements, and its multiple beneficial effects have been long recognized, although the molecular basis for these properties have remained unknown. The recent discoveries of the endogenous conversion of DHA to D-series resolvins, Protectins/Neuroprotectins, and more recently to the maresins, 82 have provided a new basis for the health benefits of DHA.
Resolvin D2 (RvD2, 27) was originally identified during resolution, 4 and it is biosynthesized from docosahexaenoic acid (DHA) via sequential lipoxygenation and epoxide hydrolysis. Recently, we established the complete stereochemistry and actions of RvD2, and also investigated whether it preserves host immune function to facilitate resolution of inflammatory sepsis.

The results indicated that new DHA derived molecules reduced cytokine IL-1β production by human glioma cells stimulated with the cytokine TNFα and importantly that DHA stored in the brain is converted to the new molecules.

DHA is a precursor to novel potent protective mediators and that 10, 17-docosatriene carried potent anti-inflammatory activity.

Circulating levels of EPA and DHA and potentially other omega-3 essential fatty acids166 in humans play an important role in regulating the time course of resolution and production of resolvins and Protectins. These mechanisms of exudate resolution and utilization of edema-supplied EPA and DHA imply a rapid utilization of dietary EPA and DHA once these substrates have reached circulation.

DHA is well appreciated to be enriched in neural systems, where it is esterified into membrane phospholipids and then, on activation, is released for production of neuroprotectins D1.