The nuclear receptor Nurr1 regulates the expression and activity of PPARγ in human pro-inflammatory macrophages

Abstract Nurr1 is a member of the orphan nuclear receptor family NR4A that modulates inflammation in several cell lineages through inhibition NF-κB signaling pathway. was found to be able interact with peroxisome proliferator-activated (PPAR)γ, as well recruited PPARG promoter LPS-activated microglial cells; however, functional relationship between and PPARγ not clearly established. Here, we aimed investigate role on activity human macrophages. Blood monocytes were cultured GM-CSF or M-CSF generate pro- (GM-MDMs) anti-inflammatory (M-MDMs) macrophages, respectively. GM-MDMs showed enhanced expression both compared M-MDMs, they preferentially located at cytoplasmic (Nurr1) (PPARγ) compartments. activation agonist rosiglitazone did modify expression. Conversely, C-DIM12 increased This concomitant two target genes, CD36 PLIN2, while silencing led decrease amounts transcripts. Co-treatment synergistically transcriptional PPARγ, whereas alone had no effect. agonists exerted effects GM-MDMs, also synergistic combined form. In sum, our data suggests positively regulates least partially induction expression, which may represent novel mechanism targeting metabolic pathways inflammation. Supported by grants from Secretaría de Educación Pública-Consejo Nacional Ciencia y Tecnología (SEP-CONACYT, #A1-S-9430)