Оn the role of pro-fibrous cytokines in the pathogenesis of localized scleroderma

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The content and skin distribution of the transforming growth factor β 1 (TGF-β 1), transforming growth factor-β receptor type I receptor (TGF-βRI) and platelet-derived growth factor receptor a (PDGFR-α), which are key fibrosis mediators, were examined in ten patients with localized scleroderma and ten healthy volunteers by using the immunohistochemistry method. A reduced derma concentration of TGF-β 1+ cells (р = 0.007) and increased amount of TGF-βRI+ (р = 0.001) and PDGFR-α+ (р < 0.001) cells was discovered in the patients vs. the control group. Te reduced amount of TGF-β 1 in the affected loci can be apparently explained by its reduced production by cells taking part in the immune inflammation. Increased expression of TGF-βRI receptors (р = 0.001) and PDGFR-α in the foci of localized scleroderma confirms their important role in the pathogenesis of the disease and activation of the fibrosis process in the skin.

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О роли профиброзных цитокинов в патогенезе локализованной склеродермии


  1. Chen K., See A., Shumack S. Epidemiology and pathogenesis of sclero-derma. Australas J Dermatol 2003; 44(1): 1—7.
  2. Yamamoto T. Scleroderma — pathophysiology. Eur J Dermatol 2009; 19 (1): 14—24.
  3. Badea I., Taylor M., Rosenberg A., Foldvari M. Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis. Rheumatology 2009; 48(3): 213—221.
  4. Ignotz R.A., Endo T., Massagué J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem 1987; 262: 14(15): 6443—6446.
  5. Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol 1990; 6: 597—641.
  6. Gay S., Trabandt A., Moreland L.W. et al. Growth factors, extracellular matrix and oncogenes in scleroderma. Arthritis Rheum 1992; 35; 3: 304—310.
  7. Wrana J.L., Attisano L., Wiesel R. et al. Mechanism of activation of the TGF-β receptor. Nature 1994; 370: 6488: 341—347.
  8. Bonner J.C. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 2004; 15(4): 255—273.
  9. Trojanowska M. Role of PDGF in fibrotic diseases and systemic sclerosis. Rheumatology 2008; 47 (Suppl 5): v2—4.
  10. Andrae J., Gallini R., Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008 22(10): 1276—1312.
  11. Higley H., Persichitte K., Chu S. et al. Immunocytochemical localization and serologic detection of transforming growth factor beta 1. Association with type I procollagen and imflammatory cell markers in diffuse and limited systemic sclerosis, morphea and Raynaud's phenomenon. Arthritis Rheum 1994; 37: 2: 278—288.
  12. Querfeld C., Eckes B., Huerkamp C. et al. Expression TGF-β1, -β2 and -β3 in localized and systemic scleroderma. J Dermatol Sci 1999; 21: 13—22.
  13. Gilmour T.K., Wilkinson B., Breit S.N. et al. Analysis of dendritic cell populations using a revised histological staging of morphoea. Br J Dermatol 2000; 143(6): 1183—1192. Литература
  14. Vuorio T., Kähäri V.M., Black C. et al. Expression of osteonectin, decorin and transforming growth factor-beta 1 genes in fibroblasts cultured from patients with systemic sclerosis and morphea. J Rheumatol 1991; 18(2): 247—251.
  15. Farrell A.M., Dean D., Charnock M. et al. Distribution of transforming growth factor-β isoforms TGF-β1, TGF-β2 and TGF-β3 and vascular endothelial growth factor in vulvar lichen sclerosus. J Reproductional Medicine 2001 46; 2: 117—124.
  16. Restrepo J.F., Guzman R., Rodriguez G. et al. Expression of transforming growth factor-beta and platelet-derived growth factor in linear scleroderma. Biomédica 2003; 23: 4: 408—415.
  17. Oikarinen A., Sandberg M., Hurskainen T. et al. Collagen biosynthesis in lichen sclerosus et atrophicus studied by biochemical and in situ hybridization techniques. Acta Derm Venereol Suppl (Stockh) 1991; 162: 3-12.
  18. Blobe G.C., Schiemann W.P., Lodish H.F. Role of transforming growth factor β in human diseases. N Engl J Med 2000; 342: 1350—1358.
  19. Kawakami T., Ihn H., Xu W. et al.: Increased expression of TGF-beta receptors by scleroderma fibroblasts: evidence for contribution of autocrine TGF-beta signaling to scleroderma phenotype. J Invest Dermatol 1998; 110: 47—51.
  20. Ярилин А.А. Основы иммунологии: Учебник. М: Медицина 1999; 608.
  21. Кетлинский С.А., Калинина Н.М. Цитокины мононуклеарных фагоцитов в регуляции реакции воспаления и иммунитета. Иммунология 1995; 3: 30—44.
  22. Yin L., Morita A.I., Tsuji T. The Crucial Role of TGF-b in the Age-Related Alterations Induced by Ultrviolet A Irradiation. J Invest Dermatol 2003; 120: 4: 703—705.
  23. Dziadzio M., Smith R.E., Abraham D.J. et al. Circulating levels of active transforming growth factor beta1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score. Rheumatol 2005; 44: 12: 1518—1524.
  24. Giacomelli R., Cipriani P., Danese C. et al. Peripheral blood mononuclear cells of patients with systemic sclerosis produce increased amounts of interleukin 6, but not transforming growth factor beta 1. J Rheumatol 1996; 23: 2: 291—296.
  25. Scala E., Pallotta S., Frezzolini A. et al. Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. Clin Exp Immunol 2004; 138: 540—546.
  26. Apostolou I., Verginis P., Kretschmer K. et al. Peripherally induced Treg: mode, stability, and role in specific tolerance. J Clin Immunol 2008; 28: 6: 619—624.
  27. Marie J.C., Letterio J.J., Gavin M. et al. TGF-1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. JEM 2005; 201: 7(4): 1061—1067.
  28. Pyzik M., Piccirillo C.A. TGF-1 modulates Foxp3 expression and regulatory activity in distinct CD4+ T cell subsets. J Leukoc Biol 2007; 82: 335—346.
  29. Taylor A.W. Review of the activation of TGF-beta in immunity. J Leukoc Biol 2009; 85: 1: 29—33.
  30. Radstake T.R.D.J., van Bon L., Broen J. et al. Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFβ expression. PLoS ONE 2009; 4: 6: e5981.
  31. Antiga E., Quaglino P., Bellandi S. et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol 2010; 162: 5: 1056—1063.
  32. Kubo M., Ihn H., Yamane K. et al. Up-regulated expression of transform-ing growth factor beta receptors in dermal fibroblasts in skin sections from patients with localized scleroderma. Arthritis Rheum 2001; 44: 3: 731—734.
  33. Klareskog L., Gustafsson R., Scheynius A. et al. Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis. Arthritis Rheum 1990; 33: 10: 1534—1541.
  34. Yamakage A., Kikuchi K., Smith E.A. et al. Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts. J Exp Med 1992; 175: 5: 1227—1234.


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