Clear Search sequence regions

  • ALX (2)
  • cell (6)
  • endothelium (1)
  • FPR2 (2)
  • human (3)
  • lipid (2)
  • lipoxin a4 (7)
  • lipoxins (2)
  • lung (6)
  • mice knockout (1)
  • palmitoyl (12)
  • phospholipid (2)
  • receptor 2 (2)
  • RhoA GTPase (1)
  • rna (1)
  • sn (11)
  • toll like receptors (1)
  • tumor necrosis factor- α (2)
  • vitro (1)
  • Sizes of these terms reflect their relevance to your search.

    Oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) generates a group of bioactive oxidized phospholipid products with a broad range of biological activities. Barrier-enhancing and anti-inflammatory effects of OxPAPC on pulmonary endothelial cells are critical for prevention of acute lung injury caused by bacterial pathogens or excessive mechanical ventilation. Anti-inflammatory properties of OxPAPC are associated with its antagonistic effects on Toll-like receptors and suppression of RhoA GTPase signaling. Because OxPAPC exhibits long-lasting anti-inflammatory and lung-protective effects even after single administration in vivo, we tested the hypothesis that these effects may be mediated by additional mechanisms, such as OxPAPC-dependent production of anti-inflammatory and proresolving lipid mediator, lipoxin A4 (LXA4). Mass spectrometry and ELISA assays detected significant accumulation of LXA4 in the lungs of OxPAPC-treated mice and in conditioned medium of OxPAPC-exposed pulmonary endothelial cells. Administration of LXA4 reproduced anti-inflammatory effect of OxPAPC against tumor necrosis factor-α in vitro and in the animal model of lipopolysaccharide-induced lung injury. The potent barrier-protective and anti-inflammatory effects of OxPAPC against tumor necrosis factor-α and lipopolysaccharide challenge were suppressed in human pulmonary endothelial cells with small interfering RNA-induced knockdown of LXA4 formyl peptide receptor-2 (FPR2/ALX) and in mFPR2-/- (mouse formyl peptide receptor 2) mice lacking the mouse homolog of human FPR2/ALX. This is the first demonstration that inflammation- and injury-associated phospholipid oxidation triggers production of anti-inflammatory and proresolution molecules, such as LXA4. This lipid mediator switch represents a novel mechanism of OxPAPC-assisted recovery of inflamed lung endothelium. © 2017 American Heart Association, Inc.


    Yunbo Ke, Noureddine Zebda, Olga Oskolkova, Taras Afonyushkin, Evgeny Berdyshev, Yufeng Tian, Fanyong Meng, Nicolene Sarich, Valery N Bochkov, Ji Ming Wang, Anna A Birukova, Konstantin G Birukov. Anti-Inflammatory Effects of OxPAPC Involve Endothelial Cell-Mediated Generation of LXA4. Circulation research. 2017 Jul 21;121(3):244-257

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 28522438

    View Full Text