For statistical analysis, the cell population was considered positive for PS externalisation

g normal epithelial cells, extravascular lymphocytes and plasma cells, and endothelial cells can express SAA; activation by pro-inflammatory cytokines can induce its expression in monocytes/macrophages, THP-1 monocytoid cells, smooth muscle cells and endothelial cells. Elevated levels of SAA are found in patients with infections, and clinical studies associate changes in SAA levels with progress of chronic inflammatory diseases with inflammatory components such as diabetes, cardiovascular disease, rheumatoid arthritis and neoplasia. SAA3 is primarily associated with high density lipoprotein in the circulation but is also deposited in inflammatory lesions. In atheroma, it is seen in endothelial cells, SMC, macrophage-derived “foam cells”, adventitial macrophages and adipocytes and SAA overexpression in apolipoprotein E2/2 mice increased plasma levels of interleukin -6, tumour necrosis factor-a and chemokine ligand-2 and accelerated progression of atherosclerosis. Since our initial studies describing cytokine and tissue factor induction by LBH589 biological activity SAA-activated monocytes/macrophages, together with its ability to promote endothelial cell 22022974 dysfunction, there is increasing interest in mechanisms relating to SAA’s pro-inflammatory function. SAA induces proinflammatory cytokines in neutrophils, monocytes and lymphocytes, and is a leukocyte chemoattractant. Several receptors are implicated, including the receptor for advanced glycation end products , formyl peptide receptor-like -1 and -2, toll-like receptor 2 and -4, and scavenger receptors CLA-1/SR-B1 and CD36 that modulate innate immune responses to several ligands. Recent studies suggest that in macrophages, four signaling pathways involving nuclear factor-kB and three mitogenactivated protein kinase may contribute to cytokine production. S100A12, S100A8 and S100A9, are a subset of S100 Ca2+-binding proteins elevated in serum from patients with various inflammatory conditions. S100A12 is constitutively expressed in neutrophils and is inducible in peripheral blood monocytes by lipopolysaccharide and TNF-a, and in human macrophages by IL-6. S100A12 is present in foam cells and macrophages in atherosclerotic lesions, in neutrophils in rheumatoid synovial lining, in eosinophils and macrophages in airway tissue from asthmatic lungs, and in infiltrating neutrophils and macrophages in chronic inflammatory bowel disease. High circulating levels of S100A12 are 1 S100A12 Blunts Monocyte Cytokine Induction by SAA present in sera from patients with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis and Kawasaki disease. Pro-inflammatory functions for SAA and S100A12 are reported, and they may share common receptors and signal transduction pathways, such as via RAGE and/or a pertussis toxin-sensitive G-protein-coupled receptor . Interactions of SAA with RAGE and with CD36 are implicated in cytokine induction. SAA induction of TF is partially mediated by RAGE on 7751958 monocytes, and on endothelial cells via FPRL-1, a human G-PCR with low affinity for N-formyl peptides; the p38 and extracellular signal-regulated kinases 1/2 MAPK, and NF-kB pathways are implicated in activation. Functions first described for S100A12 suggested a proinflammatory role, although recent studies indicate pleiotropic activities. S100A12 at low concentrations is chemotactic for neutrophils, monocytes and mast cells; it provokes mast cell activation and leukocyte recruitment in vivo, possibly involving a G-PCR. S100A12