PloS one, 2016-11, Vol.11 (11), p.e0167468-e0167468
2016
Details
- Autor(en) / Beteiligte
- Titel
- High-Density Lipoprotein (HDL) Counter-Regulates Serum Amyloid A (SAA)-Induced sPLA2-IIE and sPLA2-V Expression in Macrophages
- Ist Teil von
- PloS one, 2016-11, Vol.11 (11), p.e0167468-e0167468
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Human serum amyloid A (SAA) has been demonstrated as a chemoattractant and proinflammatory mediator of lethal systemic inflammatory diseases. In the circulation, it can be sequestered by a high-density lipoprotein, HDL, which carries cholesterol, triglycerides, phospholipids and apolipoproteins (Apo-AI). The capture of SAA by HDL results in the displacement of Apo-AI, and the consequent inhibition of SAA's chemoattractant activities. It was previously unknown whether HDL similarly inhibits SAA-induced sPLA2 expression, as well as the resultant HMGB1 release, nitric oxide (NO) production and autophagy activation. Here we provided compelling evidence that human SAA effectively upregulated the expression and secretion of both sPLA2-IIE and sPLA2-V in murine macrophages, which were attenuated by HDL in a dose-dependent fashion. Similarly, HDL dose-dependently suppressed SAA-induced HMGB1 release, NO production, and autophagy activation. In both RAW 264.7 cells and primary macrophages, HDL inhibited SAA-induced secretion of several cytokines (e.g., IL-6) and chemokines (e.g., MCP-1 and RANTES) that were likely dependent on functional TLR4 signaling. Collectively, these findings suggest that HDL counter-regulates SAA-induced upregulation and secretion of sPLA2-IIE/V in addition to other TLR4-dependent cytokines and chemokines in macrophage cultures.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0167468Titel-ID: cdi_plos_journals_1844595799
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Apolipoproteins, Autophagy, Autophagy - drug effects, Biology and Life Sciences, Cell activation, Cell death, Cells, Cultured, Chemokines, Chemokines - metabolism, Chen, Wei, Cholesterol, Cytokines, Cytokines - metabolism, Dose-Response Relationship, Drug, Emergency medical care, Enzymes, Fatty acids, Gene expression, Group II Phospholipases A2 - genetics, Group II Phospholipases A2 - metabolism, High density lipoprotein, HMGB1 protein, HMGB1 Protein - metabolism, Inflammatory diseases, Inhibition, Interleukin 6, Lipids, Lipoproteins, Lipoproteins, HDL - pharmacology, Macrophages, Macrophages - cytology, Macrophages - drug effects, Macrophages - metabolism, Male, Medical research, Medicine, Medicine and Health Sciences, Mice, Mice, Inbred C57BL, Monocyte chemoattractant protein 1, Nitric oxide, Nitric Oxide - metabolism, Peptides, Phagocytosis, Phospholipases A2, Secretory - genetics, Phospholipases A2, Secretory - metabolism, Phospholipids, RANTES, RAW 264.7 Cells, Rodents, Sepsis, Serum Amyloid A Protein - metabolism, Signal Transduction - drug effects, Signaling, Smooth muscle, TLR4 protein, Toll-Like Receptor 4 - metabolism, Toll-like receptors, Triglycerides, Up-Regulation - drug effects