title: Macrophage-derived lipid agonists of PPAR-α as intrinsic controllers of inflammation.
abstract: Macrophages are multi-faceted phagocytic effector cells that derive from circulating monocytes and undergo differentiation in target tissues to regulate key aspects of the inflammatory process. Macrophages produce and degrade a variety of lipid mediators that stimulate or suppress pain and inflammation. Among the analgesic and anti-inflammatory lipids released from these cells are the fatty acid ethanolamides (FAEs), which produce their effects by engaging nuclear peroxisome proliferator activated receptor-α (PPAR-α). Two members of this lipid family, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), have recently emerged as important intrinsic regulators of nociception and inflammation. These substances are released from the membrane precursor, N-acylphosphatidylethanolamine (NAPE), by the action of a NAPE-specific phospholipase D (NAPE-PLD), and in macrophage are primarily deactivated by the lysosomal cysteine amidase, N-acylethanolamine acid amidase (NAAA). NAPE-PLD and NAAA regulate FAE levels, exerting a tight control over the ability of these lipid mediators to recruit PPAR-α and attenuate the inflammatory response. This review summarizes recent findings on the contribution of the FAE-PPAR-α signaling complex in inflammation, and on NAAA inhibition as a novel mechanistic approach to treat chronic inflammatory disorders.
authors.affiliation: a Drug Discovery and Development, Istituto Italiano Di Tecnologia , Genoa , Italy and.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pontis
authors.affiliation: a Drug Discovery and Development, Istituto Italiano Di Tecnologia , Genoa , Italy and.
authors.forename: Alison
authors.initials: A
authors.lastname: Ribeiro
authors.affiliation: a Drug Discovery and Development, Istituto Italiano Di Tecnologia , Genoa , Italy and.
authors.forename: Oscar
authors.initials: O
authors.lastname: Sasso
authors.affiliation: a Drug Discovery and Development, Istituto Italiano Di Tecnologia , Genoa , Italy and.|b Departments of Anatomy and Neurobiology , Pharmacology and Biological Chemistry, University of California , Irvine , CA , USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008055:Lipids / Q000494:pharmacology* / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*; D047493:PPAR alpha / Q000819:agonists*
chemical_list: D008055:Lipids; D047493:PPAR alpha
keywords: Chemokines; N-acylethanolamine acid amidase; enzyme inhibitors; fatty acid ethanolamides; macrophages; nuclear receptor