A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.

Hdl Handle:
http://hdl.handle.net/10147/207645
Title:
A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.
Authors:
Mullan, Ronan Hugh; McCormick, Jennifer; Connolly, Mary; Bresnihan, Barry; Veale, Douglas James; Fearon, Ursula
Affiliation:
Education and Research Centre, St. Vincent's University Hospital, Elm Park,, Dublin 4, Ireland.
Citation:
Am J Pathol. 2010 Apr;176(4):1999-2008. Epub 2010 Mar 19.
Journal:
The American journal of pathology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207645
DOI:
10.2353/ajpath.2010.090014
PubMed ID:
20304957
Abstract:
Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.
Language:
eng
MeSH:
Antigens, CD36/metabolism/*physiology; Arthritis, Rheumatoid/*metabolism; Arthroscopy/methods; Biopsy; Dose-Response Relationship, Drug; Endothelium, Vascular/cytology; *Gene Expression Regulation; Humans; Inflammation/*pathology; Interleukin-6/metabolism; Interleukin-8/metabolism; Peptides/chemistry; Phenotype; Serum Amyloid A Protein/*biosynthesis; Synovial Membrane/*metabolism
ISSN:
1525-2191 (Electronic); 0002-9440 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMullan, Ronan Hughen_GB
dc.contributor.authorMcCormick, Jenniferen_GB
dc.contributor.authorConnolly, Maryen_GB
dc.contributor.authorBresnihan, Barryen_GB
dc.contributor.authorVeale, Douglas Jamesen_GB
dc.contributor.authorFearon, Ursulaen_GB
dc.date.accessioned2012-02-01T10:33:48Z-
dc.date.available2012-02-01T10:33:48Z-
dc.date.issued2012-02-01T10:33:48Z-
dc.identifier.citationAm J Pathol. 2010 Apr;176(4):1999-2008. Epub 2010 Mar 19.en_GB
dc.identifier.issn1525-2191 (Electronic)en_GB
dc.identifier.issn0002-9440 (Linking)en_GB
dc.identifier.pmid20304957en_GB
dc.identifier.doi10.2353/ajpath.2010.090014en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207645-
dc.description.abstractAcute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.en_GB
dc.language.isoengen_GB
dc.subject.meshAntigens, CD36/metabolism/*physiologyen_GB
dc.subject.meshArthritis, Rheumatoid/*metabolismen_GB
dc.subject.meshArthroscopy/methodsen_GB
dc.subject.meshBiopsyen_GB
dc.subject.meshDose-Response Relationship, Drugen_GB
dc.subject.meshEndothelium, Vascular/cytologyen_GB
dc.subject.mesh*Gene Expression Regulationen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInflammation/*pathologyen_GB
dc.subject.meshInterleukin-6/metabolismen_GB
dc.subject.meshInterleukin-8/metabolismen_GB
dc.subject.meshPeptides/chemistryen_GB
dc.subject.meshPhenotypeen_GB
dc.subject.meshSerum Amyloid A Protein/*biosynthesisen_GB
dc.subject.meshSynovial Membrane/*metabolismen_GB
dc.titleA role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.en_GB
dc.contributor.departmentEducation and Research Centre, St. Vincent's University Hospital, Elm Park,, Dublin 4, Ireland.en_GB
dc.identifier.journalThe American journal of pathologyen_GB
dc.description.provinceLeinster-

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