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Expression of TGFβ1 and Its Signaling Components by Peripheral Lymphocytes in Systemic Lupus Erythematosus

  • Original Paper
  • Published:
Pathology & Oncology Research

Abstract

Transforming growth factor β1 (TGFβ1) is an important immunosuppressive cytokine. Defects in its production by lymphocytes and the failure of TGFβ1 to regulate immunological functions have been described in SLE. Expression of TGFβ1 and the related signaling pathway was studied in the peripheral lymphocytes of SLE patients. The total plasma TGFβ1 level in active and inactive SLE patients compared to healthy controls was also measured. TGFβ1 and all downstream signaling elements were expressed in normal cells. However, in more than 50% of SLE patients the isolated T cell population showed no TGFβ1 mRNA expression and at least one member of the TGFβ1 pathway was also missing (TGFβ-RI, Smad2 and Smad3) in more than half of the patients. Total plasma TGFβ1 level was increased in both active and inactive SLE groups compared to normal controls (p< 0.05). These data raise questions about the availability of TGFβ1 signaling in lymphocytes in SLE patients, however, the elevated total plasma TGFβ1 level suggests that the failure of TGFβ1 effects is not the consequence of low level of this cytokine in SLE.

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Abbreviations

TGFβ1:

Transforming growth factor β1

SLE:

systemic lupus erythematosus

PBMC:

peripheral blood mononuclear cells

References

  1. Greidinger E (2001) Apoptosis in lupus pathogenesis. Front Biosci 6:1302–1325

    Article  Google Scholar 

  2. Mageed RA, Prud’homme GJ (2003) Immunopathology and the gene therapy of lupus. Gene Therapy 10:861–874

    Article  CAS  PubMed  Google Scholar 

  3. Manson JJ, Isenberg DA (2003) The pathogenesis of systemic lupus erythematosus. Neth J Med 61:343–346

    CAS  PubMed  Google Scholar 

  4. Mok CC, Lau CS (2003) Pathogenesis of systemic lupus erythematosus. J Clin Pathol 56:481–490

    Article  CAS  PubMed  Google Scholar 

  5. Derynck R, Zhang Ying E (2003) Smad-dependent and Smad-independent pathways in TGFb family signaling. Nature 425:577–584

    Article  CAS  PubMed  Google Scholar 

  6. Jackson M, Ahmad Y, Bruce IN, Coupes B, Brenchley P (2006) Activation of transforming growth factor- β1 and early atherosclerosis in systemic lupus erythematosus. Arthritis Research and Therapy 8:R81

    Google Scholar 

  7. Horwitz DA, Gray D, Ohtsuka K (1999) Role of NK cells and TGFb in the regulation of T-cell-dependent antibody production in health and autoimmune disease. Microbes Infect 1:1305–1311

    Article  CAS  PubMed  Google Scholar 

  8. Lebman DA, Edmiston JS (1998) The role of TGFb in growth, differentiation and maturation of B lymphocytes. Microbes Infect 1:1297–304

    Article  Google Scholar 

  9. Schuster N, Krieglstein K (2002) Mechanisms of TGFb-mediated apoptosis. Cell Tissue Res 307:1–14

    Article  CAS  PubMed  Google Scholar 

  10. Tótth Á, Sebestyén A, Barna G, Nagy K, Göndör A, Bocsi J, Mihalik R, Peták I, Houghton J, Kopper L (2001) TGFb induces caspase-dependent but death-receptor independent apoptosis in lymphoid cells. Anticancer Res 21:1207-1212

    PubMed  Google Scholar 

  11. Sakaguchi S, Sakaguchi N, Takahashi T (2001) Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 182:18

    Article  CAS  PubMed  Google Scholar 

  12. Zheng SG, Wang JH, Gray JD, Soucier H, Horwitz DA (2004) Natural and induced CD4+CD25+ cells educate CD4+CD25- cells to develop suppressive activity: the role of IL-2, TGFb and IL-10. J Immunol 172:5213–5221

    CAS  PubMed  Google Scholar 

  13. Horwitz DA, Gray D, Ohtsuka K, Hirokawa M, Takahashi T (1997) The immunoregulatory effects of NK cells: the role of TGFb and implications for autoimmunity. Immunology Today 18:538–542

    Article  CAS  PubMed  Google Scholar 

  14. Derynck R, Akhurst RJ, Balmain A (2001) TGFb signaling in tumor suppression and cancer progression. Nature Genetics 29:117–129

    Article  CAS  PubMed  Google Scholar 

  15. Massague J, Gomis RR (2006) The logic of TGFb signaling. FEBS Letters 580:2811–2820

    Article  CAS  PubMed  Google Scholar 

  16. Ohtsuka K, Gray D, Stimmler MM, Toro B, Horwitz DA (1998) Decreased production of TGFb by Lymphocytes from Patients with Systemic Lupus Erythematosus. J Immunol 160:2539–2545

    CAS  PubMed  Google Scholar 

  17. Linker-Israeli M, Quismorio FP Jr, Horwitz DA (1990) CD8+ lymphocytes from patients with systemic lupus erythematosus sustain rather than suppress spontaneous polyclonal IgG production and synergize with CD4+ cells to support autoantibody synthesis. Arthritis Rheum 33:1216–1225

    CAS  PubMed  Google Scholar 

  18. Liu MF, Wang CR, Fung LL, Wu CR (2004) Decreased CD4+CD25+ T cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus. Scand J Immunol 59:198–202

    Article  PubMed  Google Scholar 

  19. Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S (2005) Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol 175:8392–8400

    CAS  PubMed  Google Scholar 

  20. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271

    Article  CAS  PubMed  Google Scholar 

  21. Bombardier CD, Gladman D, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI, a disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  CAS  PubMed  Google Scholar 

  22. Lu L, Cheng H, Sung P, Yeh J, Shiue Y, Chen A (2004) Single-nucleotide polymorphisms of transforming growth factor-β1 gene in Taiwanese patients with systemic lupus erythematosus. J Microbiol Immunol Infect 37:145–152

    CAS  PubMed  Google Scholar 

  23. Schotte H, Willeke P, Rust S, Assmann G, Domschke W, Gaubitz M, Schluter B (2003) The transforming growth factor-β1 gene polymorphism (G915C) in not associated with systemic lupus erythematosus. Lupus 12:86–92

    Article  CAS  PubMed  Google Scholar 

  24. Higashi T, Kyo S, Inoue M, Tani H, Saijoh K (2006) Novel functional single nucleotide polymorphisms in the latent transforming growth factor-β1 binding protein-1 L promoter: effect on latent latent transforming growth factor-β1 binding protein-1 L expression level and possible prognostic significance in ovarian cancer. J Mol Diagn 8:342–350

    Article  CAS  PubMed  Google Scholar 

  25. McKnight AJ, Savage DA, Patterson CC, Sadlier D, Maxwell AP (2007) Resequencing of genes for transforming growth factor β1 type 1 and 2 receptors and association analysis of variants with diabetic nephropathy. BMC Medical Genetics 8:5

    Article  PubMed  Google Scholar 

  26. Robak E, Wozniacka A, Sysa-Jedrzejowska A, Stepien H, Robak T (2001) Serum levels of angiogenic cytokines in systemic lupus erythematosus and their correlation with disease activity. Eur Cytokine Netw 12:445–452

    CAS  PubMed  Google Scholar 

  27. Ruiz-Arguelles GJ, Ruiz-Arguelles A, Lobato-Mendizabal E, Diaz-Gomez F, Pacheco-Pantoja E, Denkard C, Alarcon-Segovia D (1991) Disturbances in the tissue plasminogen activator/plasminogen inhibitor (TPA/PAI) system in systemic lupus erythematosus. Am J Hematol 37:9

    Article  CAS  PubMed  Google Scholar 

  28. Cuchacovich R, Singh R, Cuellar M, Espinoza LR (2001) Distinct pattern of gene expression by DNA microarray in peripheral blood mononuclear cells of rheumatoid arthritis and psoriatc arthritis patients treated with TNF-antagonists or methotrexate. Arthritis Rheumatism 44(suppl):2949

    Google Scholar 

  29. Drynda S, Kühne C, Kekow J (2002) Soluble TNF receptor treatment does not affect raised TGFb levels in rheumatoid arthritis. Ann Rheum Dis 61:667–669

    Article  Google Scholar 

  30. Sjöwall C, Ernerudh J, Bengtsson AA, Sturfelt G, Skogh T (2004) Reduced anti- TNFα autoantibody levels coincide with flare in systemic lupus erythematosus. J Autoimmun 22:315–323

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Science Foundation of Hungary, Ministry of Welfare and Ministry of Education and Culture, Hungary (OTKA (F048380, TS049887) and Békésy Foundation (118/2001).

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Authors and Affiliations

  1. I. Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085, Budapest, Hungary

    Eszter Kohut, Melinda Hajdu, László Kopper & Anna Sebestyén

  2. Central Laboratory of Immunology, National Medical Center, Semmelweis University, Budapest, Hungary

    Péter Gergely

  3. Institute of Hematology and Immunology, National Medical Center, Budapest, Hungary

    László Gopcsa, Katalin Kilián & Katalin Pálóczi

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  1. Eszter Kohut
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  2. Melinda Hajdu
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  4. László Gopcsa
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  7. László Kopper
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  8. Anna Sebestyén
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Correspondence to Anna Sebestyén.

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Kohut, E., Hajdu, M., Gergely, P. et al. Expression of TGFβ1 and Its Signaling Components by Peripheral Lymphocytes in Systemic Lupus Erythematosus. Pathol. Oncol. Res. 15, 251–256 (2009). https://doi.org/10.1007/s12253-008-9119-8

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  • DOI: https://doi.org/10.1007/s12253-008-9119-8

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