title: The NR4A subfamily of nuclear receptors: potential new therapeutic targets for the treatment of inflammatory diseases.
abstract: Prolonged inflammatory response contributes to the pathogenesis of chronic disease-related disturbances. Among nuclear receptors (NRs), the orphan NR4A subfamily, which includes Nur77 (NR4A1), Nurr1 (NR4A2) and NOR1 (NR4A3), has recently emerged as a therapeutic target for the treatment of inflammation. Areas covered: This review focuses on the capacity of NR4A receptors to counter-regulate the development of the inflammatory response, with a special focus on the molecular transrepression mechanisms. Expert opinion: Recent studies have highlighted the role of NR4A receptors as significant regulators of the inflammatory response. NR4A receptors are rapidly induced by inflammatory stimuli, thus suggesting that they are required for the initiation of inflammation. Nevertheless, NR4A anti-inflammatory properties indicate that this acute regulation could be a protective reaction aimed at resolving inflammation in the later stages. Therefore, NR4A receptors are involved in a negative feedback mechanism to maintain the inflammatory balance. However, the underlying mechanisms are not entirely clear. Only a small number of NR4A-target genes have been identified, and the transcriptional repression mechanisms are only beginning to emerge. Despite further research is needed to fully understand the role of NR4A receptors in inflammation, these NRs should be considered as targets for new therapeutic approaches to inflammatory diseases.
authors.affiliation: a Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Pere Virgili Health Research Institute (IISPV) and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)-Instituto de Salud Carlos III, Faculty of Medicine and Health Sciences , Rovira i Virgili University , Reus , Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodríguez-Calvo
authors.affiliation: b Heart Diseases Biomedical Research Group, Inflammatory and Cardiovascular Disorders Program , Hospital del Mar Medical Research Institute (IMIM), Parc de Salut Mar , Barcelona , Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Tajes
authors.affiliation: c Department of Pharmacology, Toxicology and Therapeutic Chemistry, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Institut de Recerca Pediàtrica-Hospital Sant Joan de Déu, and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)-Instituto de Salud Carlos III, Faculty of Pharmacy, Diagonal 643 , University of Barcelona , Barcelona , Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539882:NR4A2 protein, human; C490412:NR4A3 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone
keywords: Chemokines; NF-κB; NR4A; cytokines; inflammation; transactivation; transrepression