Title:G-Protein Coupled Receptors Involved in the Resolution of Inflammation: Ligands and Therapeutic Perspectives
VOLUME: 20 ISSUE: 20
Author(s):Margherita Mastromarino, Enza Lacivita*, Nicola A. Colabufo and Marcello Leopoldo
Affiliation:Dipartimento di Farmacia - Scienze del Farmaco, Universita degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Dipartimento di Farmacia - Scienze del Farmaco, Universita degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Dipartimento di Farmacia - Scienze del Farmaco, Universita degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Dipartimento di Farmacia - Scienze del Farmaco, Universita degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari
Keywords:Resolution of inflammation, pro-resolving specialized mediators, GPCRs, FPR2, GPR32, ChemR23, GPR18.
Abstract:Dysregulated inflammation is a central pathological process in diverse disease states, including
neurodegenerative disorders. The recent concept of “resolution of inflammation” is offering a
conceptual change for the diagnosis and the development of new therapeutic approaches for chronic
inflammatory diseases. Resolution of inflammation terminates the inflammatory response promoting
the return to tissue homeostasis through the action of several classes of mediators, termed specialized
pro-resolving lipid mediators (SPMs), that include lipoxins, resolvins, protectins, and maresins. SPMs
provide “stop signals” that reduce the number of immune cells at the site of insult and increase the
clearance of apoptotic cells through phagocytosis. SPMs elicit their effects through the interaction with
specific G-protein coupled receptors (GPCRs). The elucidation of the pathways downstream of the
GPCRs involved in the resolution of chronic inflammation is opening novel opportunities to generate
novel anti-inflammatory agents. This review focuses on the SPMs and the receptors through which
their effects are mediated. The medicinal chemistry of the modulators of the GPCRs involved in the
resolution of inflammation will be illustrated, by highlighting the potential for developing new antiinflammatory
drugs.
