Lipoxins and aspirin-triggered lipoxins in resolution of inflammation

Eur J Pharmacol. 2015 Aug 5:760:49-63. doi: 10.1016/j.ejphar.2015.03.083. Epub 2015 Apr 18.

Abstract

The resolution of the inflammatory response is highly regulated by the timely biosynthesis of a number of endogenous lipid mediators. Among these, lipoxins (LX) and their 15-epimers, aspirin triggered lipoxins (ATL) derived by the lipoxygenase (LO) route of arachidonic acid metabolism. In particular, they are formed and released by cells expressing 5-, 12- and 15-LO such as leukocytes, platelets, vascular endothelium and epithelium, alone or during transcellular interactions. ATL biosynthesis requires cyclooxygenase-2 acetylation by aspirin. LX and ATL exert potent bioactions on leukocytes, vascular and epithelial cells to stop inflammation and promote resolution. They have shown to be beneficial in a broad spectrum of preclinical models of disease as well as in some clinical trials. Counter-regulatory signaling by LXA4 and 15-epi-LXA4 follows the activation of a G protein-coupled receptor, termed ALX/FPR2, which is emerging as a key anti-inflammatory receptor.

Keywords: Efferocytosis; Inflammation; Lipoxin; Lipoxygenase; Polymorphysm; Promoter; Receptor; Resolution; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aspirin / toxicity*
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Lipoxins / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Inflammation Mediators
  • Lipoxins
  • lipoxin A4
  • Aspirin