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Published on: November 26, 2018
beta(2)-Microglobulin increases the expression of vascular cell adhesion molecule on human synovial fibroblasts
M I Jaradat1, C T Schnizlein-Bick, G K Singh
1Department of Medicine, Indiana University School of Medicine, and Richard Roudebush VAMC, Indianapolis, Indiana, USA.
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.
Conclusion:
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.
Insights
beta(2)-microglobulin (beta(2)m) increases vascular cell adhesion molecule-1 (VCAM-1) expression in synovial fibroblasts, contributing to beta(2)m amyloidosis pathogenesis. This highlights the role of synovial fibroblasts in the disease.
Area of Science:
- Rheumatology
- Nephrology
- Cell Biology
Background:
- Beta(2)-microglobulin (beta(2)m) amyloidosis is a debilitating articular disease common in dialysis patients.
- The pathogenesis is linked to adhesion molecules, similar to other arthritic conditions.
- Synovial fibroblasts are investigated for their role in this inflammatory process.
Purpose of the Study:
- To determine if beta(2)m directly upregulates vascular cell adhesion molecule-1 (VCAM-1) expression in synovial fibroblasts.
- To examine the impact of advanced glycation end products (AGEs) on beta(2)m-induced VCAM-1 expression.
- To investigate the functional consequence of VCAM-1 upregulation on immune cell adhesion.
Main Methods:
- Human synovial fibroblasts were cultured and treated with beta(2)m, with and without AGE modification.
- VCAM-1 expression was quantified using immunohistochemistry, flow cytometry, Western blotting, and Northern blotting.
- Peripheral blood mononuclear cell adhesion to treated synovial fibroblasts was assessed.
Main Results:
- Beta(2)m significantly increased VCAM-1 protein expression in a dose-dependent manner.
- While beta(2)m increased VCAM-1 mRNA levels, AGE modification of beta(2)m did not alter this effect.
- Synovial fibroblast adhesion of peripheral blood mononuclear cells was enhanced by beta(2)m.
Conclusions:
- Beta(2)m directly stimulates VCAM-1 expression in synovial fibroblasts.
- Synovial fibroblasts play a crucial role in the pathogenesis of beta(2)m amyloidosis.
- Targeting VCAM-1 may offer a therapeutic strategy for beta(2)m amyloidosis.
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