PPARγand the Innate Immune System Mediate the Resolution of Inflammation

Abstract

The resolution of inflammation is an active and dynamic process, mediated in large part by the innate immune system. Resolution represents not only an increase in anti-inflammatory actions, but also a paradigm shift in immune cell function to restore homeostasis. PPARγ, a ligand activated transcription factor, has long been studied for its anti-inflammatory actions, but an emerging body of literature is investigating the role of PPARγand its ligands (including thiazolidinediones, prostaglandins, and oleanolic acids) in all phases of resolution. PPARγcan shift production from pro- to anti-inflammatory mediators by neutrophils, platelets, and macrophages. PPARγand its ligands further modulate platelet and neutrophil function, decreasing trafficking, promoting neutrophil apoptosis, and preventing platelet-leukocyte interactions. PPARγalters macrophage trafficking, increases efferocytosis and phagocytosis, and promotes alternative M2 macrophage activation. There are also roles for this receptor in the adaptive immune response, particularly regarding B cells. These effects contribute towards the attenuation of multiple disease states, including COPD, colitis, Alzheimer’s disease, and obesity in animal models. Finally, novel specialized proresolving mediators—eicosanoids with critical roles in resolution—may act through PPARγmodulation to promote resolution, providing another exciting area of therapeutic potential for this receptor.