Bioactive products generated by Group V sPLA2 hydrolysis of LDL activate macrophages to secrete pro-inflammatory cytokines

Boris B. Boyanovsky, Xia Li, Preetha Shridas, Manjula Sunkara, Andrew J. Morris, Nancy R. Webb

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Objective: Previous studies have established that hydrolysis of LDL by Group V secretory phospholipase A2 (GV sPLA2) generates a modified particle capable of inducing macrophage foam cell formation. The aim of the present study was to determine whether GV sPLA2-hydrolyzed LDL (GV-LDL) produces pro-atherogenic effects in macrophages independent of cholesterol accumulation. Methods and results: J-774 cells incubated with GV-LDL produced more TNF-α and IL-6 compared to cells incubated with control-LDL. Indirect immunofluorescence showed that GV-LDL but not control-LDL induced nuclear translocation of NFκB. Inhibitors of NFκB activation, effectively blocked cytokine production induced by GV-LDL. Control-LDL and GV-LDL were separated from albumin present in reaction mixtures by ultracentrifugation. The albumin fraction derived from GV-LDL contained 80% of the FFA generated and was more potent than the re-isolated GV-LDL in inducing pro-inflammatory cytokine secretion. Linoleic acid (18:2) and oleic acid (18:1) were the most abundant FFAs generated, whereas newly formed lyso-PCs contained 14:0 (myristic), 16:1 (palmitic), and 18:2 fatty acyl groups. Experiments with synthetic FFA showed that 18:1 induced J-774 cells to secrete TNF-α and IL-6. Conclusions: These results indicate that in addition to promoting atherosclerotic lipid accumulation in macrophages, GV sPLA2 hydrolysis of LDL leads to activation of NFκB, a key regulator of inflammation.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalCytokine
Volume50
Issue number1
DOIs
StatePublished - Apr 2010

Keywords

  • Atherosclerosis
  • Inflammation
  • Lipoprotein modification
  • NFκB
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Biochemistry
  • Immunology and Allergy
  • Immunology

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