Peroxisome Proliferator-activated Receptor- as a Regulator of Lung Inflammation and Repair

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that regulate the expression of genes involved in a variety of biological processes, including lipid metabolism and insulin sensitivity. Members of the PPAR family—in particular, PPAR—have more recently been shown to broadly regulate inflammatory and reparative responses. PPARis expressed in both alveolar macrophages and neutrophils, and the ligand-dependent activation of this receptor results in suppression of leukocyte effector responses, including cytokine production, the elaboration of reactive oxygen and nitrogen species, and migratory responses. In addition to antiinflammatory effects, PPARregulates diverse processes in lung stromal/parenchymal cells, including cell growth, differentiation, and apoptosis. Studies examining in vivo effects of PPARhave produced complex and at times conflicting results. However, evidence to date generally suggests that PPARfunctions to dampen inflammation and injury in various animal models of acute lung injury. PPARmay also play an important role in other inflammatory/immune lung diseases, including ischemiareperfusion injury, allergic airway inflammation, and cancer. The role of PPARin human lung diseases, including acute lung injury, requires further study.