Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-5-20
pubmed:abstractText
Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
184
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6427-37
pubmed:meshHeading
pubmed-meshheading:20435930-Adult, pubmed-meshheading:20435930-Aged, pubmed-meshheading:20435930-Aged, 80 and over, pubmed-meshheading:20435930-Animals, pubmed-meshheading:20435930-Arthritis, Experimental, pubmed-meshheading:20435930-Arthritis, Rheumatoid, pubmed-meshheading:20435930-Blotting, Western, pubmed-meshheading:20435930-Cell Movement, pubmed-meshheading:20435930-Endothelial Cells, pubmed-meshheading:20435930-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:20435930-Female, pubmed-meshheading:20435930-Humans, pubmed-meshheading:20435930-Inflammation, pubmed-meshheading:20435930-Male, pubmed-meshheading:20435930-Mice, pubmed-meshheading:20435930-Mice, SCID, pubmed-meshheading:20435930-Middle Aged, pubmed-meshheading:20435930-Monocytes, pubmed-meshheading:20435930-Neovascularization, Pathologic, pubmed-meshheading:20435930-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20435930-Serum Amyloid A Protein, pubmed-meshheading:20435930-Synovial Membrane, pubmed-meshheading:20435930-Transplantation Chimera, pubmed-meshheading:20435930-Young Adult
pubmed:year
2010
pubmed:articleTitle
Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.
pubmed:affiliation
Dublin Academic Medical Centre, University College Dublin, Dublin, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't