1. High-Density Lipoprotein (HDL) Counter-Regulates Serum Amyloid A (SAA)-Induced sPLA2-IIE and sPLA2-V Expression in Macrophages.
- Author
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Zhu, Shu, Wang, Yongjun, Chen, Weiqiang, Li, Wei, Wang, Angelina, Wong, Sarabeth, Bao, Guoqiang, Li, Jianhua, Yang, Huan, Tracey, Kevin J., D’Angelo, John, and Wang, Haichao
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HIGH-density lipoprotein receptors ,AMYLOID ,MACROPHAGES ,PELVIC inflammatory disease ,LIPOPROTEINS - Abstract
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 sPLA
2 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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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