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 PPARγ and its ligands (including thiazolidinediones, prostaglandins, and oleanolic acids) in all phases of resolution. PPARγ can shift production from pro- to anti-inflammatory mediators by neutrophils, platelets, and macrophages. PPARγ and its ligands further modulate platelet and neutrophil function, decreasing trafficking, promoting neutrophil apoptosis, and preventing platelet-leukocyte interactions. PPARγ 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 mediators—eicosanoids with critical roles in resolution—may act through PPARγ modulation to promote resolution, providing another exciting area of therapeutic potential for this receptor.

Cystic Fibrosis Lung Immunity: The Role of the Macrophage

“…Much of the regulator process of efferocytosis goes back to the inverse relationships between PPARg and NF-kB again regulating the phenotypic characteristic of the MΦs contribution to the inflammatory process. PPARγ drives the M2 whereas the NF-kβ drives the M1 75 . The PPARs as retinoic acid based lipid scavenger receptors are important in the process associated with surfactant and lipid metabolism 76 .…”

Detecting Perturbed Subpathways towards Mouse Lung Regeneration Following H1N1 Influenza Infection

“…Moving forward, "Cytokine-cytokine receptor interaction" pathway has been shown to participate into activating the immune and inflammatory response to prevent from virus infections [24]. Moreover, "PPAR signaling" and "complement and coagulation" cascades have been suggested to repair excessive tissue damage by exhibiting anti-inflammatory functions [27]. Finally, with respect to "leukocyte transedothelial migration", it has been suggested that circulating blood leukocytes migrate to tissue injury and infection site to terminate the primary inflammatory trigger and thus assist tissue repair [28,29].…”

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

“…PPARγ’s expression by various cells of the immune system underscores its prominent role in inflammatory responses [14, 16, 73, 74]. Following initial recognition as a regulator of monocytes/macrophage function in atherosclerosis [73], PPARγ is now known to regulate functions of other inflammation-associated cell types [4, 13, 74, 75] in various disease and disease model contexts [4, 73, 75].…”

“…Following initial recognition as a regulator of monocytes/macrophage function in atherosclerosis [73], PPARγ is now known to regulate functions of other inflammation-associated cell types [4, 13, 74, 75] in various disease and disease model contexts [4, 73, 75]. Furthermore, many inflammatory conditions are associated with alterations in PPARγ expression and activity, and such changes are believed to contribute significantly to several diseases [5, 76].…”