title: High-Density Lipoprotein (HDL) Counter-Regulates Serum Amyloid A (SAA)-Induced sPLA2-IIE and sPLA2-V Expression in Macrophages.
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 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.
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York, United States of America.|The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York, United States of America.|The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York, United States of America.|The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Angelina
authors.initials: A
authors.lastname: Wang
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Sarabeth
authors.initials: S
authors.lastname: Wong
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Department of General Surgery, Tangdu Hospital, The 4th Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Bao
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: D'Angelo
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, New York, United States of America.|The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Haichao
authors.identifier: http://orcid.org/0000-0002-0211-9000
authors.initials: H
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054501:Group II Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000235:genetics / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018925:Chemokines; D016207:Cytokines; D024243:HMGB1 Protein; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D054501:Group II Phospholipases A2; D054497:Phospholipases A2, Secretory