OBJECTIVE: Serum amyloid A (A- @entity5475 ) is an acute-phase protein with cytokine-like properties implicated in the pathogenesis of @entity309 ( @entity309 ), @entity731 , @entity6 and @entity195 . This study characterises the mechanism of A- @entity5475 -induced cytoskeletal rearrangement and migration in synovial fibroblasts and microvascular endothelial cells ( @entity1 dermal endothelial cells; HDEC). METHODS: Immunohistology and immunofluorescence were used to examine avb3 and b1-integrins, filamentous actin (F-actin) and focal adhesion expression in @entity309 synovial tissue (RAST) and @entity309 synovial fibroblast cells (RASFC). A- @entity5475 -induced avb3 and b1-integrin binding was measured by adhesion assay. Cytoskeletal rearrangement and   -GTPase activation following A- @entity5475 stimulation was examined using dual immunofluorescent staining for F-actin/vinculin staining, pull down assays and immunoblotting for @entity5605 and @entity3547 . Cell growth, invasion/migration, angiogenesis and actin formation were examined in the presence or absence of specific @entity5180 and @entity5605 inhibitors ( @entity7186 and 187-1). RESULTS: avb3, b1-integrin and F-actin predominantly localised to vascular endothelium and lining layer cells in RAST, compared with @entity571 and normal control synovial tissue. A- @entity5475 significantly increased avb3 and b1 binding in RASFC. A- @entity5475 induced cytoskeletal disassembly, loss of focal adhesions and filopodia formation in RASFC and HDEC. A- @entity5475 significantly induced @entity5605 activation but failed to promote @entity3547 activation in HDEC and synovial fibroblast cells. Blockade of @entity5180 and @entity5605 inhibited A- @entity5475 -induced cell growth, invasion/migration, actin cytoskeletal rearrangement and angiogenesis. CONCLUSIONS: These data show a novel mechanism for A- @entity5475 -induced cell migrational events in @entity309 mediated via cytoskeletal signalling pathways.

Acute serum amyloid A regulates cytoskeletal rearrangement, cell matrix interactions and promotes cell migration in XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity571 :: ('MESH:D010003', 'Disease') :: ['osteoarthritis'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity7186 :: ('MESH:C487513', 'Chemical') :: ['NSC23766'] @entity3547 :: ('387', 'Gene') :: ['RhoA'] @entity5605 :: ('998', 'Gene') :: ['Cdc42'] @entity195 :: ('MESH:D000544', 'Disease') :: ["Alzheimer's disease"] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity5475 :: ('6287', 'Gene') :: ['SAA'] @entity5180 :: ('5879', 'Gene') :: ['Rac1', 'Rac-1'] @entity309 :: ('MESH:D001172', 'Disease') :: ['rheumatoid arthritis', 'RA']
@entity309 :: (MESH:D001172,Disease) :: ['rheumatoid arthritis']
