title: Determination of role of thromboxane A2 in rheumatoid arthritis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Mao-Jie
authors: MJ
authors: Wang
authors: Central Laboratory, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Yu
authors: Y
authors: Huang
authors: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Run-Yue
authors: RY
authors: Huang
authors: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Xiu-Min
authors: XM
authors: Chen
authors: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Ying-Yan
authors: YY
authors: Zhou
authors: Central Laboratory, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Wan-Lin
authors: WL
authors: Yu
authors: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Yong-Liang
authors: YL
authors: Chu
authors: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, China.
authors: Qing-Chun
authors: QC
authors: Huang
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D013928:Thromboxane A2 / Q000097:blood* / Q000378:metabolism
chemical_list: D013928:Thromboxane A2; D002097:C-Reactive Protein