Thesis

The pro- or anti-inflammatory effects of oxidized or chlorinated lipids and its signalling mechanisms

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Awarding institution
  • University of Strathclyde
Date of award
  • 2012
Thesis identifier
  • T13371
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Abstract
  • It is currently well accepted that atherosclerosis is an inflammatory disease and accumulation of oxidized low density lipoprotein (OxLDL) is a principal risk factor for this disease. Since the finding that oxidized phospholipids (OxPLs) is active components of OxLDL, many studies have demonstrated their pro- and antiinflammatory effects as well as signalling mechanisms. In comparison, less is known about chlorinated lipids, although several reports show that they are found in atherosclerotic lesions and inflammatory loci, and induce mainly pro-inflammatory effects. This study investigated the role of chlorinated lipids on pro-inflammatory cytokine production and the signalling mechanisms induced by these modified lipids, in comparison with OxPLs. Treatment of myeloid (U937) cells with 1-stearoyl-2- oleoyl-sn-3-glycerophosphocholine chlorohydrin (SOPC ClOH) but not its native lipid enhanced the effect of lipopolysaccharide (LPS)-induced interleukin-8 (IL-8) and treatment with 2-chlorohexadecanal (2-ClHDA) inhibited LPS-induced tumor necrosis-alpha (TNF-α) production. However, treatment of these compounds alone did not increase the level of IL-8 and TNF-α)pression. Using mouse fibrosarcoma cells (L929sA) that were stably transfected with nuclear factor-kappaB (NF-kB) dependent promoter, it was demonstrated that SOPC ClOH and 2-ClHDA did not stimulate NF-kB-driven genes activity and did not inhibit TNFα-induced NF-kB driven genes activity. SOPC ClOH treatment of human embryonic kidney 293 (HEK 293) cells overexpressing PPARα-driven gene expression. However, treatment of these cells with native SOPC and 2-ClHDA did not induce similar effects. In addition, treatment of human umbilical vein endothelial cells (HUVECs) with SOPC ClOH and 2-ClHDA did not induce degradation of Ikappa B alpha (IkB-α) or expression of mitogen activated protein kinases (MAPKs), and pretreatment with either SOPC ClOH or 2-ClHDA did not inhibit LPS-mediated activation of NF-kB and MAPK pathways. In conclusion, phospholipid induced pro-inflammatory effects and stimulated PPRE-driven gene activity in cells overexpressing PPARα whereas 2-ClHDA induced an anti-inflammatory effect. The effects were different to those observed with short-chain OxPLs, showing that the nature of the oxidative modification is important in determining cellular response
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  • Strathclyde theses - ask staff. Thesis no. : T13371
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Date Created
  • 2012
Former identifier
  • 989146

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