Lipid mediators: lipoxin and aspirin-triggered 15-epi-lipoxins.
Lipoxins (LX) and their 15-epimers, aspirin triggered lipoxins (ATL) are emerging as major promoters of resolution of the inflammatory reaction. These eicosanoids, that carry a tetraene chromophore, derive from sequential lipoxygenase (LO) metabolism of arachidonic acid. Three principal routes of LX/ATL biosynthesis have been uncovered. One involves cooperation between 15- and 5-LO, one other requires interactions between 12- and 5-LO and a third is characterized by 5-LO transformation of intermediary products generated by aspirin-acetylated cyclooxygenase (COX)-2. Thus, in a large majority of cases the biosynthesis of these eicosanois requires transcellular metabolic exchange during cell-cell interactions. LX and ATL are rapidly metabolized and inactivated by monocyte 15-hydroxyprostaglandin dehydrogenase (PGDH). A number of stable analogs that resist inactivation and retain biological activity has been synthesized. Accumulating evidence suggests that these analogs may have a potential therapeutic impact in a variety of diseases characterized by neutrophil-mediated persistent inflammation, such as reperfusion injury, gastro-intestinal and renal inflammatory disorders, periodontitis. Clinical evaluation of LXA4 and 15-epi-LXA4 formation and their pharmacological regulation may be now achieved using recently developed ELISA assays, that allow large-scale measurements in human biological fluids.
Romano
Mario
M
Department of Biomedical Sciences, Aging Research Center, Ce.S.I., Gabriele D'Annunzio University Foundation, Via dei Vestini, 31, 66013, Chieti, Italy. mromano@unich.it
D000107:Acetylation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000627:therapeutic use; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001168:Arthritis / Q000188:drug therapy / Q000378:metabolism; D001241:Aspirin / Q000378:metabolism*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D044045:Lipoxins / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine; D010518:Periodontitis / Q000188:drug therapy / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D044045:Lipoxins; C040527:lipoxin A4; D016718:Arachidonic Acid; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D001241:Aspirin