Skip to main content

Advertisement

Log in

Bcl-xL expression in vivo in rheumatoid synovium

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

To examine the expression of the apoptosis regulatory protein, Bcl-xL, in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-xL was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-xL. Bcl-xL expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-xL expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r s=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-xL expression in rheumatoid patients. Bcl-xL may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Yamamura Y, Gupta R, Morita Y et al (2001) Effector function of resting T cells: activation of synovial fibroblasts. J Immunol 166:2270–2275

    PubMed  CAS  Google Scholar 

  2. Zvaifler NJ, Boyle D, Firestein GS (1994) Early synovitis-synoviocytes and mononuclear cells. Semin Arthritis Rheum 23:11–16

    Article  PubMed  CAS  Google Scholar 

  3. Rudin CM, Thompson CB (1997) Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med 48:267–281

    Article  PubMed  CAS  Google Scholar 

  4. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    PubMed  CAS  Google Scholar 

  5. Nagata S, Golstein P (1995) The Fas death factor. Science 267:1449–1456

    PubMed  CAS  Google Scholar 

  6. Nakajima T, Aono H, Hasunuma T et al (1995) Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum 38:485–491

    PubMed  CAS  Google Scholar 

  7. Firestein GS, Yeo M, Zvaifler NJ (1995) Apoptosis in rheumatoid arthritis synovium. J Clin Invest 96:1631–1638

    PubMed  CAS  Google Scholar 

  8. Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911

    PubMed  CAS  Google Scholar 

  9. Basanez G, Zhang J, Chau BN et al (2001) Pro-apoptotic cleavage products of Bcl-xL form cytochrome c-conducting pores in pure lipid membranes. J Biol Chem 276:31083–31091

    Article  PubMed  CAS  Google Scholar 

  10. Korsmeyer SJ (1999) BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59:1693s–1700s

    PubMed  CAS  Google Scholar 

  11. Perlman H, Georganas C, Pagliari LJ, Koch AE, Haines K 3rd, Pope RM (2000) Bcl-2 expression in synovial fibroblasts is essential for maintaining mitochondrial homeostasis and cell viability. J Immunol 164:5227–5235

    PubMed  CAS  Google Scholar 

  12. Kharbanda S, Pandey P, Schofield L et al (1997) Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis. Proc Natl Acad Sci U S A 94:6939–6942

    Article  PubMed  CAS  Google Scholar 

  13. Fang W, Weintraub BC, Dunlap B et al (1998) Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing. Immunity 9:35–45

    Article  PubMed  CAS  Google Scholar 

  14. Bovia F, Nabili-Tehrani AC, Werner-Favre C, Barnet M, Kindler V, Zubler RH (1998) Quiescent memory B cells in human peripheral blood co-express bcl-2 and bcl-x(L) anti-apoptotic proteins at high levels. Eur J Immunol 28:4418–4423

    Article  PubMed  CAS  Google Scholar 

  15. Hayashida K, Shimaoka Y, Ochi T, Lipsky PE (2000) Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism. J Immunol 164:1110–1116

    PubMed  CAS  Google Scholar 

  16. Zhang X, Li L, Choe J et al (1996) Up-regulation of Bcl-xL expression protects CD40-activated human B cells from Fas-mediated apoptosis. Cell Immunol 173:149–154

    Article  PubMed  CAS  Google Scholar 

  17. Lakics V, Medvedev AE, Okada S, Vogel SN (2000) Inhibition of LPS-induced cytokines by Bcl-xL in a murine macrophage cell line. J Immunol 165:2729–2737

    PubMed  CAS  Google Scholar 

  18. Lindblad S, Hedfors E (1985) Intraarticular variation in synovitis. Local macroscopic and microscopic signs of inflammatory activity are significantly correlated. Arthritis Rheum 28:977–986

    PubMed  CAS  Google Scholar 

  19. Yamanishi Y, Firestein GS (2001) Pathogenesis of rheumatoid arthritis: the role of synoviocytes. Rheum Dis Clin North Am 27:355–371

    Article  PubMed  CAS  Google Scholar 

  20. Mountz JD, Hsu H, Matsuki Y, Zhang H (2001) Apoptosis and rheumatoid arthritis: past, present, and future directions. Curr Rheumatol Rep 3:70–78

    PubMed  CAS  Google Scholar 

  21. Matsumoto S, Muller-Ladner U, Gay RE, Nishioka K, Gay S (1996) Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol 23:1345–1352

    PubMed  CAS  Google Scholar 

  22. Dechanet J, Merville P, Durand I, Banchereau J, Miossec P (1995) The ability of synoviocytes to support terminal differentiation of activated B cells may explain plasma cell accumulation in rheumatoid synovium. J Clin Invest 95:456–463

    Article  PubMed  CAS  Google Scholar 

  23. Perry ME, Mustafa Y, Wood SK, Cawley MI, Dumonde DC, Brown KA (1997) Binucleated and multinucleated forms of plasma cells in synovia from patients with rheumatoid arthritis. Rheumatol Int 17:169–174

    Article  PubMed  CAS  Google Scholar 

  24. Berek C, Kim HJ (1997) B-cell activation and development within chronically inflamed synovium in rheumatoid and reactive arthritis. Semin Immunol 9:261–268

    Article  PubMed  CAS  Google Scholar 

  25. Reparon-Schuijt CC, van Esch WJ, van Kooten C, Levarht EW, Breedveld FC, Verweij CL (1998) Functional analysis of rheumatoid factor-producing B cells from the synovial fluid of rheumatoid arthritis patients. Arthritis Rheum 41:2211–2220

    Article  PubMed  CAS  Google Scholar 

  26. Drossaers-Bakker KW, Zwinderman AH, Vlieland TP et al (2002) Long-term outcome in rheumatoid arthritis: a simple algorithm of baseline parameters can predict radiographic damage, disability, and disease course at 12-year followup. Arthritis Rheum 47:383–390

    Article  PubMed  CAS  Google Scholar 

  27. Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ (2002) Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis Rheum 46:906–912

    Article  PubMed  CAS  Google Scholar 

  28. Di Girolamo N, Visvanathan K, Lloyd A, Wakefield D (1997) Expression of TNF-alpha by human plasma cells in chronic inflammation. J Leukoc Biol 61:667–678

    PubMed  Google Scholar 

  29. Tu Y, Renner S, Xu F et al (1998) BCL-X expression in multiple myeloma: possible indicator of chemoresistance. Cancer Res 58:256–262

    PubMed  CAS  Google Scholar 

  30. Sioud M, Mellbye O, Forre O (1998) Analysis of the NF-kappa B p65 subunit, Fas antigen, Fas ligand and Bcl-2-related proteins in the synovium of RA and polyarticular JRA. Clin Exp Rheumatol 16:125–134

    PubMed  CAS  Google Scholar 

  31. Hilbers I, Hansen T, Petrow PK et al (2003) Expression of the apoptosis accelerator Bax in rheumatoid arthritis synovium. Rheumatol Int 23:75–81

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors have declared no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Busteed.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Busteed, S., Bennett, M.W., Molloy, C. et al. Bcl-xL expression in vivo in rheumatoid synovium. Clin Rheumatol 25, 789–793 (2006). https://doi.org/10.1007/s10067-005-0191-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-005-0191-0

Keywords

Navigation