Identification and structure elucidation of the pro‐resolving mediators provides novel leads for resolution pharmacology

Abstract

Inflammatory diseases are a major socio‐economic burden, with the incidence of such conditions on the rise, especially in western societies. For decades, the primary treatment paradigm for many of these conditions was to develop drugs that inhibit or antagonize the production and biological actions of molecules that were thought to be the culprits in propagating disease; these include cytokines and eicosanoids. This approach is effective in controlling disease propagation; however, long‐term exposure to these anti‐inflammatories is also associated with many side effects, some of which are severe, including immune‐suppression. The discovery that termination of self‐limited acute inflammation is an active process orchestrated by endogenous mediators, including the essential fatty acid‐derived resolvins, protectins and maresins, has provided novel opportunities for the design of therapeutics that control inflammation with a lower burden of side effects. This is because at variance to anti‐inflammatories, pro‐resolving mediators do not completely inhibit inflammatory responses; instead, these mediators reprogramme the immune response to accelerate the termination of inflammation, facilitating the regain of function. The scope of this review is to highlight the biological actions of these autacoids and their potential utility as lead compounds in developing resolution pharmacology‐based therapeutics. Linked Articles This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc

Free fatty acid receptor 4 is a nutrient sensor that resolves inflammation to maintain cardiac homeostasis

“…injection of 18-HEPE attenuated remodeling post-TAC (49). Interestingly, 18-HEPE is also the precursor for E-series resolvins (RvE1, RvE2, and RvE3), a class of pro-resolving oxylipins (50). E-resolvins signal through ERV1/ChemR23, an orphan GPR that binds to and is activated by both E-resolvins and the endogenous peptide chemerin, suggesting a potential mechanism to explain EPA-mediated inflammation resolving effects (51).…”

Shifting the paradigm from inhibitors of inflammation to resolvers of inflammation in periodontitis

“…24 The discovery of the molecular identity of these SPMs and their receptors launched the field of "resolution pharmacology." 26 Resolution pharmacology has key differences from inflammation inhibitor pharmacology. SPMs are naturally occurring molecules in the body that function as agonists for receptors.…”

(Re) Solving Repair After Myocardial Infarction

“…Human artery segments and primary cultured human vascular cells generate D-series resolvins and maresins when the relevant fatty acid precursors are present, and in the absence of leukocytes ( Chatterjee et al, 2017 ). Recently, novel molecules termed maresin conjugates in tissue regeneration (MCTR), protectin conjugates in tissue regeneration (PCTR), and resolvin conjugates in tissue regeneration (RCTR) are identified as other pro-repair inducers ( Dalli et al, 2014 , 2015b ; Dalli and Serhan, 2018 ). These new compounds could represent new therapeutical treatments for patients with myocardial infarction.…”