beta(2)-Microglobulin increases the expression of vascular cell adhesion molecule on human synovial fibroblasts.
BACKGROUND
beta(2)-Microglobulin (beta(2)m) amyloidosis is a destructive articular disease that affects patients on dialysis. The disease presentation is similar to other forms of arthritis in which adhesion molecules are felt to be pathogenic. Therefore, we hypothesized that beta(2)m directly increases the expression of vascular cell adhesion molecule-1 (VCAM-1) by synovial fibroblasts. We also examined the effect of alteration of beta(2)m by advanced glycation end products on this cellular response.


METHODS
Human synovial fibroblasts were isolated and incubated with beta(2)m with and without alteration with advanced glycation end products. VCAM-1 expression was determined by immunohistochemistry, flow cytometry, and Western blot and Northern blot analyses.


RESULTS
beta(2)m increased the protein expression of VCAM-1 by synovial fibroblasts in a dose-dependent manner. beta(2)m altered with advanced glycation end products had no effect. However, all forms of beta(2)m increased VCAM-1 mRNA. beta(2)m also increased the adhesion of peripheral blood mononuclear cells to synovial fibroblasts.


CONCLUSIONS
beta2m directly increases the expression of VCAM-1 by synovial fibroblasts, indicating that synovial fibroblasts may play a key role in the pathogenesis of beta(2)m amyloidosis.
Jaradat
M I
MI
Department of Medicine, Indiana University School of Medicine, and Richard Roudebush VAMC, Indianapolis, Indiana, USA.
Schnizlein-Bick
C T
CT
Singh
G K
GK
Moe
S M
SM
D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007596:Joints / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000494:pharmacology*
D017931:DNA Primers; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D001613:beta 2-Microglobulin