The novel lipid mediator PD1n-3 DPA: An overview of the structural elucidation, synthesis, biosynthesis and bioactions

Hansen, Trond Vidar; Dalli, Jesmond; Serhan, Charles N.

doi:10.1016/j.prostaglandins.2017.06.003

Cited by 48 publications

(29 citation statements)

References 61 publications

(97 reference statements)

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“…Using a systems approach, we The Journal of Clinical Investigation like aspirin, changes the enzyme's catalysis to produce predominantly R-epimer-containing intermediates, exemplified by novel 13-series resolvins (RvTs) from vascular n-3DPA (26). The complete stereochemistry and biosynthesis of each SPM are established (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43), as are epoxy-intermediates of maresins and protectins (36).…”

Section: Specialized Novel Mediators In Resolutionmentioning

confidence: 99%

“…These n-3 immunoresolvents are biosynthesized ( Figure 2) in three families: resolvin n-3DPA , protectin n-3DPA , and maresin n-3DPA , each demonstrating potent pro-resolving actions (27) in human subjects (78). Rapid advances in the organic synthesis of SPMs from n-3DPA and their matching to endogenous mediators (36,79) facilitated demonstration of potent protection by protectin D1 n-3DPA and resolvin D5 n-3DPA in colitis (80). Human and mouse tissues treated with the statin atorvastatin convert n-3DPA to RvTs (26).…”

Section: Spms Promote Resolution In Sterile Versus Infectious Inflammmentioning

confidence: 99%

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Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators

Serhan¹,

Levy

2018

Journal of Clinical Investigation

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Countless times each day, the acute inflammatory response protects us from invading microbes, injuries, and insults from within, as in surgery-induced tissue injury. These challenges go unnoticed because they are self-limited and naturally resolve without progressing to chronic inflammation. Peripheral blood markers of inflammation are present in many common diseases, including inflammatory bowel disease, cardiovascular disease, neurodegenerative disease, and cancer. While acute inflammation is protective, excessive swarming of neutrophils amplifies collateral tissue damage and inflammation. Hence, understanding the mechanisms that control the resolution of acute inflammation provides insight into preventing and treating inflammatory diseases in multiple organs. This Review focuses on the resolution phase of inflammation with identification of specialized pro-resolving mediators (SPMs) that involve three separate biosynthetic and potent mediator families, which are defined using the first quantitative resolution indices to score this vital process. These are the resolvins, protectins, and maresins: bioactive metabolomes that each stimulate self-limited innate responses, enhance innate microbial killing and clearance, and are organ-protective. We briefly address biosynthesis of SPMs and their activation of endogenous resolution programs as terrain for new therapeutic approaches that are not, by definition, immunosuppressive, but rather new immunoresolvent therapies.

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Section: Specialized Novel Mediators In Resolutionmentioning

confidence: 99%

Section: Spms Promote Resolution In Sterile Versus Infectious Inflammmentioning

confidence: 99%

Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators

Serhan¹,

Levy

2018

Journal of Clinical Investigation

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976

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“…2) derived from vascular n-3DPA [26]. The stereochemical biosynthesis of each of the major SPM is established [31][32][33][34], as are their epoxide-containing intermediates (vide infra) eMaR and 16(17)PD1 [35,36].…”

Section: New Chemical Signals: Specialized Pro-resolving Mediator Supmentioning

confidence: 99%

Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation

2019

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Excessive chronic inflammation is linked to many diseases and considered a stress factor in humans (Robbins Pathologic Basis of Disease. Philadelphia: W.B. Saunders Co., 1999, Proc Natl Acad Sci USA, 2008, 105: 17949, Immunity, 44, 2016, 44: 463, N Engl J Med, 2011, 364: 656). Today, the resolution of inflammation is widely recognized as a cellular biochemically active process involving biosynthesis of a novel superfamily of endogenous chemical signals coined specialized pro‐resolving mediators (SPMs; Nature, 2014, 510:92). Herein, we review recent evidence, indicating a role for the vagus nerve and vagotomy in the regulation of lipid mediators. Vagotomy reduces pro‐resolving mediators, including the lipoxins, resolvins, protectins and maresins, delaying resolution in mouse peritonitis. Vagotomy also delays resolution of Escherichia coli infection in mice. Specifically, right vagus regulates peritoneal Group 3 innate lymphoid cell (ILC‐3) number and peritoneal macrophage responses with lipid mediator profile signatures with elevated pro‐inflammatory eicosanoids and reduced resolvins, including the novel protective immunoresolvent agonist protectin conjugate in tissue regeneration1 (PCTR1). Acetylcholine upregulates PCTR biosynthesis, and administration of PCTR1 to vagotomized mice restores tissue resolution and host responses to E. coli infections. Results obtained with human vagus ex vivo indicate that vagus can produce both pro‐inflammatory eicosanoids, such as prostaglandins and leukotrienes, as well as the SPM. Electrical stimulation of human vagus in vitro reduces both prostaglandins and leukotrienes and enhances resolvins and the other SPM. These results elucidate a host protective mechanism mediated by vagus stimulation of SPM that includes resolvins and PCTR1 to regulate myeloid antimicrobial functions and resolution of infection. Moreover, they define a new pro‐resolution of inflammation reflex operative in mice and human tissue that involves a vagus SPM circuit.

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“…In particular, the emerging field of specialized pro-resolving mediators provides promising and exciting targets for new anti-inflammatory, neuroprotective and anti-infective drugs and natural products [9] [10] [11] [12] [13]. Specialized pro-resolving mediators are highly interesting in that metabolites of not just DHA and EPA, but also n-3DPA and n-6DPA can actively resolve inflammation at very low concentrations, proving new insight into the numerous health benefits epidemiologically associated with diets high in fish and/or total LC-PUFA [14] [15] [16] [17].…”

Section: Introductionmentioning

confidence: 99%

Gradient Temperature Raman Spectroscopy of Fatty Acids with One to Six Double Bonds Identifies Specific Carbons and Provides Systematic Three Dimensional Structures

Broadhurst¹,

Schmidt²,

Nguyen³

et al. 2018

JBPC

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Specialized pro-resolving mediators provide promising targets for new drugs and natural products. Much work has been accomplished on the structure/ function of the lipoxygenase and cyclooxygenase enzymes but not on the substrates. A better visualization of three-dimensional lipid structures will allow increased refinement of the interactions that produce the pro-resolving mediators, and lead to improvements in synthetic pathways. We present systematic analysis of oleic (18:1n-9), linoleic (18:2n-6), alpha-linolenic (18:3n-3), arachidonic (20:4n-6), docosapentaenoic (22:5n-3), and docosahexaenoic (22:6n-3) acids. Continuous gradient temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy. GTRS can identify and differentiate specific carbon chain sites, finally allowing Raman analysis to explain why the long-chain polyunsaturated fatty acids (LC-PUFA) exhibit such extreme functional differences despite minimal changes in chemical structure. Detailed vibrational analysis of the important frequency ranges 1450 -1200 cm −1 (includes CH 2 bending and twisting) and 1750 -1425 cm −1 (includes C=C stretching and C-C stretching plus H-C in-plane rocking) shows for the first time that each molecule has its own characteristic set of modes with only some redundancy/commonality. The number and frequency of modes correlates with three-dimensional molecular structure, not the degree of unsaturation. The high degree of specificity of lipoxygenase and cyclooxygenase enzymes should be reconsidered in light of the fact that individual sites on the polyunsaturated fatty acid chain are

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The novel lipid mediator PD1n-3 DPA: An overview of the structural elucidation, synthesis, biosynthesis and bioactions

Cited by 48 publications

References 61 publications

Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators

Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators

Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation

Gradient Temperature Raman Spectroscopy of Fatty Acids with One to Six Double Bonds Identifies Specific Carbons and Provides Systematic Three Dimensional Structures

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