Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation

Fiona H. Greig, Simon Kennedy, Corinne M. Spickett

Research output: Contribution to journalArticle

Abstract

Oxidized phospholipids, such as the products of the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory cytokine production, cell adhesion and migration, proliferation, apoptosis, and necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain Toll-like receptors (TLRs) induced by microbial products that normally leads to inflammation. They also have protective effects via the stimulation of small GTPases and induce up-regulation of antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized phospholipids interact with several cellular receptors, including scavenger receptors, platelet-activating factor receptors, peroxisome proliferator-activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways.
LanguageEnglish
Pages266-280
Number of pages15
JournalFree Radical Biology and Medicine
Volume52
Issue number2
Early online date31 Oct 2011
DOIs
Publication statusPublished - 15 Jan 2012

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Cell signaling
Phospholipids
Inflammation
Toll-Like Receptors
Pathology
Scavenger Receptors
Peroxisome Proliferator-Activated Receptors
Monomeric GTP-Binding Proteins
Macrophages
Cell adhesion
Endothelial cells
Cellular Structures
Bioactivity
Cell Adhesion
Smooth Muscle Myocytes
Cell Movement
Muscle
Animals
Necrosis
Up-Regulation

Keywords

  • animals
  • atherosclerosis
  • cell membrane
  • cell proliferation
  • chlorohydrins
  • Endothelium
  • humans
  • inflammation
  • inflammation mediators
  • LDL lipoproteins
  • oxidation-reduction
  • peroxisome proliferator-activated receptors
  • phospholipids
  • signal transduction
  • toll-like receptors

Cite this

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title = "Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation",
abstract = "Oxidized phospholipids, such as the products of the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory cytokine production, cell adhesion and migration, proliferation, apoptosis, and necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain Toll-like receptors (TLRs) induced by microbial products that normally leads to inflammation. They also have protective effects via the stimulation of small GTPases and induce up-regulation of antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized phospholipids interact with several cellular receptors, including scavenger receptors, platelet-activating factor receptors, peroxisome proliferator-activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways.",
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Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation. / Greig, Fiona H.; Kennedy, Simon; Spickett, Corinne M.

In: Free Radical Biology and Medicine, Vol. 52, No. 2, 15.01.2012, p. 266-280.

Research output: Contribution to journalArticle

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