RRC ID 67260
Author Wang MJ, Huang Y, Huang RY, Chen XM, Zhou YY, Yu WL, Chu YL, Huang QC.
Title Determination of role of thromboxane A2 in rheumatoid arthritis.
Journal Discov Med
Abstract INTRODUCTION:To date, the etiology of rheumatoid arthritis (RA) remains largely unknown, and the therapies are still unsatisfactory. The biosynthesis of thromboxane A2 (TxA2) is increased in RA patients, suggesting a role of TxA2 in RA pathology.
METHODS:RA patients were divided into two groups, DMARDs and non-DMARDs, according to their use of disease-modifying antirheumatic drugs (DMARDs). Sera from RA patients and healthy controls were extracted and subjected to enzyme immunoassays for measurement of the thromboxane B2 (TxB2) level. The statistical correlations between serum TxB2 levels and disease activity score of 28 joints (DAS28), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) were calculated. Moreover, the effects of dual TxA2 modulator BM567 on cell proliferation as well as protein expression of α-actinin and NF-κB2 in RA fibroblast-like synovial (FLS) cells MH7A were determined by MTS assays and Western blot analysis, respectively. The effects of BM567 on mRNA expression of cyclooxygenase (COX)-2, a downstream product of NF-κB2 and an upstream enzyme of TxA2, was examined by real-time quantitative PCR experiments.
RESULTS:Serum TxB2 level was significantly higher in RA patients as compared to healthy controls. Both DAS28 score and serum TxB2 levels were slightly lower in the DMARDs group than the non-DMARDs group, without statistical significance, and there was positive correlation between these two factors. BM567 significantly suppressed cell proliferation as well as expression of α-actinin, NF-κB2, p52, and COX-2 in MH7A.
CONCLUSION:TxA2 plays an important role in RA pathology, synovial cell proliferation in particular, through an auto-regulatory feedback loop. Thus, targeting TxA2 may represent a promising add-on therapy in the treatment of RA.
Volume 19(102)
Pages 23-32
Published 2015-1-1
PMID 25636958
MeSH Adult Aged Arthritis, Rheumatoid / blood* Arthritis, Rheumatoid / metabolism C-Reactive Protein / metabolism Cell Line Cell Proliferation / physiology Female Humans Immunoenzyme Techniques Male Middle Aged Synovial Fluid / cytology Synovial Fluid / metabolism Thromboxane A2 / blood* Thromboxane A2 / metabolism
Human and Animal Cells MH7A(RCB1512)