Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

Hdl Handle:
http://hdl.handle.net/10147/254765
Title:
Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.
Authors:
Connolly, Mary; Marrelli, Alessandra; Blades, Mark; McCormick, Jennifer; Maderna, Paola; Godson, Catherine; Mullan, Ronan; FitzGerald, Oliver; Bresnihan, Barry; Pitzalis, Costantino; Veale, Douglas J; Fearon, Ursula
Affiliation:
Dublin Academic Medical Centre, University College Dublin, Dublin, Ireland.
Citation:
Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model. 2010, 184 (11):6427-37 J. Immunol.
Publisher:
Journal of immunology (Baltimore, Md. : 1950)
Journal:
Journal of immunology (Baltimore, Md. : 1950)
Issue Date:
1-Jun-2010
URI:
http://hdl.handle.net/10147/254765
DOI:
10.4049/jimmunol.0902941
PubMed ID:
20435930
Abstract:
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.
Item Type:
Article
Language:
en
MeSH:
Adult; Aged; Aged, 80 and over; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Blotting, Western; Cell Movement; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Male; Mice; Mice, SCID; Middle Aged; Monocytes; Neovascularization, Pathologic; Reverse Transcriptase Polymerase Chain Reaction; Serum Amyloid A Protein; Synovial Membrane; Transplantation Chimera; Young Adult
ISSN:
1550-6606

Full metadata record

DC FieldValue Language
dc.contributor.authorConnolly, Maryen_GB
dc.contributor.authorMarrelli, Alessandraen_GB
dc.contributor.authorBlades, Marken_GB
dc.contributor.authorMcCormick, Jenniferen_GB
dc.contributor.authorMaderna, Paolaen_GB
dc.contributor.authorGodson, Catherineen_GB
dc.contributor.authorMullan, Ronanen_GB
dc.contributor.authorFitzGerald, Oliveren_GB
dc.contributor.authorBresnihan, Barryen_GB
dc.contributor.authorPitzalis, Costantinoen_GB
dc.contributor.authorVeale, Douglas Jen_GB
dc.contributor.authorFearon, Ursulaen_GB
dc.date.accessioned2012-12-06T12:40:04Z-
dc.date.available2012-12-06T12:40:04Z-
dc.date.issued2010-06-01-
dc.identifier.citationAcute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model. 2010, 184 (11):6427-37 J. Immunol.en_GB
dc.identifier.issn1550-6606-
dc.identifier.pmid20435930-
dc.identifier.doi10.4049/jimmunol.0902941-
dc.identifier.urihttp://hdl.handle.net/10147/254765-
dc.description.abstractSerum 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.en_GB
dc.language.isoenen
dc.publisherJournal of immunology (Baltimore, Md. : 1950)en_GB
dc.rightsArchived with thanks to Journal of immunology (Baltimore, Md. : 1950)en_GB
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAnimals-
dc.subject.meshArthritis, Experimental-
dc.subject.meshArthritis, Rheumatoid-
dc.subject.meshBlotting, Western-
dc.subject.meshCell Movement-
dc.subject.meshEndothelial Cells-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInflammation-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, SCID-
dc.subject.meshMiddle Aged-
dc.subject.meshMonocytes-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshSerum Amyloid A Protein-
dc.subject.meshSynovial Membrane-
dc.subject.meshTransplantation Chimera-
dc.subject.meshYoung Adult-
dc.titleAcute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.en_GB
dc.typeArticleen
dc.contributor.departmentDublin Academic Medical Centre, University College Dublin, Dublin, Ireland.en_GB
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en_GB
dc.description.provinceLeinsteren

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