Tags

Type your tag names separated by a space and hit enter

Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is functionally active.
Arthritis Rheum. 2004 Sep; 50(9):2786-93.AR

Abstract

OBJECTIVE

To examine fibroblasts grown from the synovial fluid of rheumatoid arthritis (RA) patients for TRAIL-R2 expression, and for susceptibility to apoptosis induced by an agonistic anti-TRAIL-R2 monoclonal antibody (mAb).

METHODS

The expression of TRAIL-R2 (DR5) was determined by flow cytometry on fibroblasts grown from the synovial fluid of patients with RA, osteoarthritis (OA), seronegative arthritis, and unclassified monarthritis or oligoarthritis, and on fibroblasts from the synovial membrane of RA and OA patients. Susceptibility to apoptosis mediated by an agonistic anti-TRAIL-R2 mAb was determined by alamar blue bioassay, fluorescence microscopy (annexin V/propidium iodide staining), and caspase activation.

RESULTS

Fibroblasts grew from 35 of 50 RA synovial fluid samples, of which 26 were DR5(+) (mean [+/-SD] fluorescence intensity [MFI] 18.74 +/- 2.5). Fibroblasts also grew from 15 of 30 seronegative arthritis synovial fluid samples, 28 of 40 OA synovial fluid samples, and 8 of 20 unclassified monarthritis or oligoarthritis synovial fluid samples; all of these were DR5- (MFI 0.32 +/- 0.02). All 10 of the fibroblast lines from joint replacement surgery or synovectomy specimens of RA patients were DR5(+) (MFI 20.3 +/- 3.2). All fibroblast lines from the synovium of 10 OA patients were DR5-, as were fibroblasts from the skin of 5 healthy subjects. DR5(+) fibroblast cultures underwent apoptosis when treated in vitro with an agonistic anti-DR5 antibody.

CONCLUSION

Fibroblasts grown from the synovial fluid and synovial membrane of RA patients express TRAIL-R2 that is functionally active. An agonistic anti-TRAIL-R2 antibody that does not induce hepatocyte toxicity may be an alternative strategy for treatment of RA.

Authors+Show Affiliations

Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain. eugeniamiranda@telefonica.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15457446

Citation

Miranda-Carús, María-Eugenia, et al. "Rheumatoid Arthritis Synovial Fluid Fibroblasts Express TRAIL-R2 (DR5) That Is Functionally Active." Arthritis and Rheumatism, vol. 50, no. 9, 2004, pp. 2786-93.
Miranda-Carús ME, Balsa A, Benito-Miguel M, et al. Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is functionally active. Arthritis Rheum. 2004;50(9):2786-93.
Miranda-Carús, M. E., Balsa, A., Benito-Miguel, M., De Ayala, C. P., & Martín-Mola, E. (2004). Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is functionally active. Arthritis and Rheumatism, 50(9), 2786-93.
Miranda-Carús ME, et al. Rheumatoid Arthritis Synovial Fluid Fibroblasts Express TRAIL-R2 (DR5) That Is Functionally Active. Arthritis Rheum. 2004;50(9):2786-93. PubMed PMID: 15457446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is functionally active. AU - Miranda-Carús,María-Eugenia, AU - Balsa,Alejandro, AU - Benito-Miguel,Marta, AU - De Ayala,Carlos Pérez, AU - Martín-Mola,Emilio, PY - 2004/10/1/pubmed PY - 2004/10/27/medline PY - 2004/10/1/entrez SP - 2786 EP - 93 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 50 IS - 9 N2 - OBJECTIVE: To examine fibroblasts grown from the synovial fluid of rheumatoid arthritis (RA) patients for TRAIL-R2 expression, and for susceptibility to apoptosis induced by an agonistic anti-TRAIL-R2 monoclonal antibody (mAb). METHODS: The expression of TRAIL-R2 (DR5) was determined by flow cytometry on fibroblasts grown from the synovial fluid of patients with RA, osteoarthritis (OA), seronegative arthritis, and unclassified monarthritis or oligoarthritis, and on fibroblasts from the synovial membrane of RA and OA patients. Susceptibility to apoptosis mediated by an agonistic anti-TRAIL-R2 mAb was determined by alamar blue bioassay, fluorescence microscopy (annexin V/propidium iodide staining), and caspase activation. RESULTS: Fibroblasts grew from 35 of 50 RA synovial fluid samples, of which 26 were DR5(+) (mean [+/-SD] fluorescence intensity [MFI] 18.74 +/- 2.5). Fibroblasts also grew from 15 of 30 seronegative arthritis synovial fluid samples, 28 of 40 OA synovial fluid samples, and 8 of 20 unclassified monarthritis or oligoarthritis synovial fluid samples; all of these were DR5- (MFI 0.32 +/- 0.02). All 10 of the fibroblast lines from joint replacement surgery or synovectomy specimens of RA patients were DR5(+) (MFI 20.3 +/- 3.2). All fibroblast lines from the synovium of 10 OA patients were DR5-, as were fibroblasts from the skin of 5 healthy subjects. DR5(+) fibroblast cultures underwent apoptosis when treated in vitro with an agonistic anti-DR5 antibody. CONCLUSION: Fibroblasts grown from the synovial fluid and synovial membrane of RA patients express TRAIL-R2 that is functionally active. An agonistic anti-TRAIL-R2 antibody that does not induce hepatocyte toxicity may be an alternative strategy for treatment of RA. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15457446/Rheumatoid_arthritis_synovial_fluid_fibroblasts_express_TRAIL_R2__DR5__that_is_functionally_active_ L2 - https://doi.org/10.1002/art.20501 DB - PRIME DP - Unbound Medicine ER -