RESEARCH - Acute-phase serum amyloid A in rheumatoid arthritis

[Guest guest]

Arthritis Rheum. 2006 Jan;54(1):105-14.

Acute-phase serum amyloid A stimulation of angiogenesis, leukocyte

recruitment, and matrix degradation in rheumatoid arthritis through an

NF-kappaB-dependent signal transduction pathway.

Mullan RH, Bresnihan B, Golden-Mason L, Markham T, O'hara R, Fitzgerald O,

Veale DJ, Fearon U.

St. 's University Hospital, Dublin, and the Conway Institute of

Molecular Medicine, Dublin, Ireland.

OBJECTIVE: To examine the role of the acute-phase protein serum amyloid A

(A-SAA) in regulating cell adhesion molecule expression, leukocyte

recruitment, and angiogenesis in rheumatoid arthritis (RA). METHODS:

Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule

1 (VCAM-1), and matrix metalloproteinase 1 (MMP-1) expression was examined

in RA fibroblast-like synoviocytes (FLS) and human microvascular endothelial

cells (HMVECs) using flow cytometry and enzyme-linked immunosorbent assay

techniques. Peripheral blood mononuclear cell (PBMC) adhesion to FLS/HMVECs

was determined by flow cytometry. Angiogenesis was examined using a Boyden

chemotaxis chamber and Matrigel tubule formation. NF-kappaB/IkappaBalpha

mediation of the effects of A-SAA was investigated using a specific

NF-kappaB inhibitor and Western blotting. RESULTS: A-SAA significantly

enhanced the time- and dose-dependent expression of ICAM-1 and VCAM-1 as

effectively as interleukin-1beta/tumor necrosis factor alpha. A-SAA promoted

the adhesion of PBMCs to FLS and HMVECs. In addition, A-SAA at 10 mug/ml and

50 mug/ml significantly increased endothelial cell tube formation by 69% and

207%, respectively. At 50 mug/ml and 100 mug/ml, A-SAA increased HMVEC

migration by 188 +/- 54% and 296 +/- 71%, respectively (mean +/- SEM).

A-SAA-induced expression of VCAM-1, ICAM-1, and MMP-1 was down-regulated by

NF-kappaB inhibition. Furthermore, A-SAA induced IkappaBalpha degradation

and NF-kappaB translocation, suggesting that its proinflammatory effects are

mediated in part by NF-kappaB signaling.

CONCLUSION: Our findings demonstrate the ability of A-SAA to induce adhesion

molecule expression, angiogenesis, and matrix degradation, mechanisms that

are mediated by NF-kappaB. Targeting A-SAA and its signaling pathways may

represent a new therapeutic approach in the treatment of RA.

PMID: 16385502

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6385502 & dopt=Abstract

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org