Novel Anti-Inflammatory-Pro-Resolving Mediators and Their Receptors

Charles      N. Serhan; Sriram      Krishnamoorthy; Antonio      Recchiuti; Nan      Chiang

Abstract

Resolution of inflammation, an actively coordinated program, is essential to maintain host health. It involves effective removal of inflammatory stimuli and the spatio-temporal control of leukocyte trafficking as well as chemical mediator generation. During the active resolution process, new classes of small, local acting endogenous autacoids, namely the lipoxins, D and E series resolvins, (neuro)protectins, and maresins have been identified. These specialized proresolving lipid mediators (SPM) prevent excessive inflammation and promote removal of microbes and apoptotic cells, thereby expediting resolution and return to tissue homeostasis. As part of their molecular mechanism, SPM exert their potent actions via activating specific pro-resolving G-protein coupled receptors. Together these SPM and their receptors provide new concepts and opportunities for therapeutics, namely promoting active resolution as opposed to the conventionally used enzyme inhibitors and receptor antagonists. This approach may offer new targets suitable for drug design for treating inflammation related diseases, for the new terrain of resolution pharmacology.

Keywords: G-protein coupled receptor, inflammatory exudates, leukocytes, mediator lipidomics, omega-3 fatty acids, resolvins, trafficking, specialized proresolving lipid mediators, antagonists, TNF, prostaglandins, arthritis, lipoxins, potent chemoattractants, Protectins