PPARγ and the Innate Immune System Mediate the Resolution of Inflammation

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. PPAR gamma, 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 PPAR gamma and its ligands (including thiazolidinediones, prostaglandins, and oleanolic acids) in all phases of resolution. PPAR gamma can shift production from pro- to anti-inflammatory mediators by neutrophils, platelets, and macrophages. PPAR gamma and its ligands further modulate platelet and neutrophil function, decreasing trafficking, promoting neutrophil apoptosis, and preventing platelet-leukocyte interactions. PPAR gamma alters 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 mediator-seicosanoids with critical roles in resolution-may