Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors

Abstract

The acute inflammatory response is host protective to contain foreign invaders. Many of today’s pharmacopeia that block pro-inflammatory chemical mediators can cause serious unwanted side effects such as immune suppression. Uncontrolled inflammation is now considered a pathophysiologic basis associated with, many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity and asthma, as well as the classic inflammatory diseases, e.g. arthritis, periodontal diseases. The inflammatory response is designated to be a self-limited process that produces a superfamily of chemical mediators that stimulate resolution of inflammatory responses. Specialized proresolving mediators (SPM) uncovered in recent years are endogenous mediators that include omega-3-derived families resolvins, protectins and maresins, as well as arachidonic acid-derived (n-6) lipoxins that stimulate and promote resolution of inflammation, clearance of microbes, reduce pain and promote tissue regeneration via novel mechanisms. Here, we review recent evidence from human and preclinical animal studies, together with the structural and functional elucidation of SPM indicating the SPM as physiologic mediators and pharmacologic agonists that stimulate resolution of inflammation and infection. These results suggest that it is time to develop immunoresolvents as agonists for testing resolution pharmacology in nutrition and health as well as in human diseases and during surgery.

Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases

“…However, while formally described as inflammatory, the plietropic effects of the eicosanoids are now more deeply appreciated, and it is understood that many of the side effects of these therapies are due to blocking their production. More recently, attention has been focused on alternative eicosanoid or docosanoid metabolites that are anti-inflammatory or pro-resolving including the EpFA (for a review of specialized pro-resolving mediators (SPMs) see Chaing and Serhan, 2017). Even compounds considered as predominantly proinflammatory seem to regulate a series of events leading to resolution of inflammation.…”

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

“…Since each member of each family possesses potent pro‐resolving and anti‐inflammatory actions [reviewed in ] in the resolution phase, together they are engaged in host protection as an SPM superfamily. They each carry these defining pro‐resolving anti‐inflammatory functions, with additional properties that are both cell type‐ and organ‐specific, reflecting their stereospecific activation of cell surface receptors . The main biosynthesis routes in Fig.…”

Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1n−3 DPA

“…Essential for these advancements have been the isolation, structural elucidation, and total synthesis of specialized pro‐resolving mediators (SPMs) . SPMs display potent anti‐inflammatory and pro‐resolving actions, often in the low nanomolar range, via G protein‐coupled receptors (GPCRs) . The resolution of inflammation is now recognized to be an active process highly regulated by individual families of SPMs and is therefore seen as a biomedical paradigm shift .…”