Bioactive products generated by Group V sPLA2 hydrolysis of LDL activate macrophages to secrete pro-inflammatory cytokines
| Autor: | Nancy R. Webb, Manjula Sunkara, Preetha Shridas, Xia Li, Andrew J. Morris, Boris B. Boyanovsky |
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| Rok vydání: | 2010 |
| Předmět: |
Lipoprotein modification
Lipolysis Linoleic acid medicine.medical_treatment Immunology Biology Biochemistry Article Group V Phospholipases A2 Proinflammatory cytokine Mice chemistry.chemical_compound Albumins Chlorocebus aethiops medicine Animals Humans Immunology and Allergy Molecular Biology Foam cell Cell Nucleus Interleukin-6 Tumor Necrosis Factor-alpha Cholesterol Hydrolysis Macrophages Fatty Acids NF-kappa B Cholesterol LDL Hematology Macrophage Activation Protein Transport Cytokine chemistry COS Cells lipids (amino acids peptides and proteins) Cytokine secretion Tumor necrosis factor alpha Inflammation Mediators Protein Binding |
| Zdroj: | Cytokine. 50:50-57 |
| ISSN: | 1043-4666 |
| DOI: | 10.1016/j.cyto.2009.12.009 |
| Popis: | Objective: Previous studies have established that hydrolysis of LDL by Group V secretory phospholipase A 2 (GV sPLA 2 ) generates a modified particle capable of inducing macrophage foam cell formation. The aim of the present study was to determine whether GV sPLA 2 -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 sPLA 2 hydrolysis of LDL leads to activation of NFκB, a key regulator of inflammation. |
| Databáze: | OpenAIRE |
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