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

Am J Pathol. 2010 Apr;176(4):1999-2008. doi: 10.2353/ajpath.2010.090014. Epub 2010 Mar 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • Arthroscopy / methods
  • Biopsy
  • CD36 Antigens / metabolism
  • CD36 Antigens / physiology*
  • 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*


  • CD36 Antigens
  • Interleukin-6
  • Interleukin-8
  • Peptides
  • Serum Amyloid A Protein