Lipid Mediators: Lipoxin and Aspirin-Triggered 15-Epi-Lipoxins

Author(s): Mario Romano

Journal Name: Inflammation & Allergy - Drug Targets (Discontinued)
Formerly Current Drug Targets - Inflammation & Allergy

Volume 5 , Issue 2 , 2006


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.

Keywords: Arachidonic acid, lipoxygenase, cyclooxygenase, metabolism, inflammation, stable analogs

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Article Details

Year: 2006
Page: [81 - 90]
Pages: 10
DOI: 10.2174/187152806776383152
Price: $65

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