PPARγ structure and signaling in macrophages.

NRs have a highly conserved structure with an N-terminal transactivation domain and a DNA-binding domain and C-terminal ligand-binding domain that are connected by a hinge region. Upon activation, the NR PPARγ heterodimerizes with RXR, binds to PPREs, and initiates transcription of target genes initiating various signaling pathways in macrophages. PPARγ signaling is induced in macrophages following infection with several pathogens, including bacteria, parasites, and viruses. During infection, PPARγ signaling has been linked to increased wound-healing responses, M2 macrophages, phagocytosis, and decreased inflammation. PPARγ has also been linked to decreased apoptosis and increased lipid uptake in macrophages. Conversely, PPARγ has been linked to both reduced and increased ROS production, including increased mitochondrial ROS production in the absence of NADPH oxidase. Arg1, arginase 1; CD36, cluster of differentiaion 36; MR, mannose receptor; NADPH, nicotinamide adenine dinucleotide phosphate; NF-κb, nuclear factor kappa B; NR, nuclear receptor; PPARγ, peroxisome proliferator-activated receptor gamma; PPRE, PPAR response element; ROS, reactive oxygen species; RXR, retinoid X receptor; TNF-α, tumor necrosis factor α.