title: Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes.
abstract: OBJECTIVE
  Serum amyloid A (SAA) is a biomarker of inflammation. Elevated blood levels in cardiovascular disease and local deposition in atheroma implies a role of SAA as a mediator rather than just a marker of inflammation. This study explored SAA-induced cytokine production and secretion by mononuclear cells.
  
  
  RESULTS
  RT-PCR showed that SAA time-dependently induced cytokine mRNAs in peripheral blood mononuclear cells (PBMC) and THP-1 monocytoid cells, and dramatically increased IL-1beta, MCP-1, IL-6, IL-8, IL-10, GM-CSF, TNF, and MIP-1alpha secretion by PBMC to levels 28 to 25,000 fold above baseline, as measured with Bio-Plex kits; monocytes were the principle source. SAA induction of cytokines in monocyte-derived macrophages (MDM) was significantly higher than from monocytes from the same donors. SAA time-dependently induced transient and significant upregulation of NF-kappaB1 mRNA; inhibitor studies indicate that activation of NF-kappaB through the ERK1/2, p38 and JNK MAPKs and the PI3K pathway was involved. PBMC from 10 patients with coronary artery disease (CAD) spontaneously secreted higher levels of IL-6 and MIP-1alpha after 24h incubation than PBMC from normal controls, whereas SAA-induced levels of all cytokines were similar to controls. Aortic and coronary sinus sampling in 23 CAD patients indicated significant SAA release into the coronary circulation, not evident in 11 controls.
  
  
  CONCLUSIONS
  SAA can increase monocyte and macrophage cytokine production, possibly at sites of atherosclerosis, thereby contributing to the pro-inflammatory state in coronary artery disease.
authors.affiliation: Department of Cardiology and ANZAC Research Institute Vascular Biology Group, Concord Hospital, University of Sydney, Sydney, Australia.
authors.forename: Changjie
authors.initials: C
authors.lastname: Song
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hsu
authors.forename: Eric
authors.initials: E
authors.lastname: Yamen
authors.forename: Weixing
authors.initials: W
authors.lastname: Yan
authors.forename: Jianyi
authors.initials: J
authors.lastname: Fock
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Geczy
authors.forename: S Ben
authors.initials: SB
authors.lastname: Freedman
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000276:immunology* / Q000503:physiopathology; D003326:Coronary Circulation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases