Abstract
We sought to determine whether the spontaneous production of transforming growth factor-β (TGF-β) by peripheral blood mononuclear cells (PBMC) is increased in patients with systemic sclerosis (SSc). Culture supernatants of PBMC from SSc patients (n=88) and healthy controls (n=44) were analyzed by enzyme-linked immunosorbent assay. The production of active TGF-β1 and total (active and latent) TGF-β1 by PBMC from patients with limited cutaneous SSc (lSSc) and by PBMC from patients with diffuse cutaneous SSc (dSSc) was significantly elevated compared to the production by PBMC from normal controls. Production of active TGF-β1 by dSSc PBMC was higher than that by lSSc PBMC, although not significantly. Patients with PBMC with increased active or total TGF-β1 production showed significantly shorter disease duration than patients with PBMC with normal production levels. PBMC from patients without anticentromere antibody showed enhanced active TGF-β1 production more frequently than those from patients with anticentromere antibody. PBMC from SSc patients more frequently showed enhanced total TGF-β2 production than PBMC from normal controls. Among each leukocyte subset, spontaneous production of total TGF-β1 was significantly higher in cultured peripheral monocytes/macrophages, but not in T cells, B cells, or NK cells, from patients than from normal controls. Thus, the enhanced production of TGF-β by PBMC may contribute to the disease process in SSc
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References
Takehara K (2003) Hypothesis: pathogenesis of systemic sclerosis. J Rheumatol 30:755–759
Sato S (1999) Abnormalities of adhesion molecules and chemokines in scleroderma. Curr Opin Rheumatol 11:503–507
Denton CP, Abraham DJ (2001) Transforming growth factor- β and connective tissue growth factor: key cytokines in scleroderma pathogenesis. Curr Opin Rheumatol 13:505–511
LeRoy EC, Smith EA, Kahaleh MB, Trojanowska M, Silver RM (1989) A strategy for determining the pathogenesis of systemic sclerosis: is transforming growth factor β the answer? Arthritis Rheum 32:817–825
Sporn MB, Roberts AB (1992) Transforming growth factor- β: recent progress and new challenges. J Cell Biol 119:1017–1021
Snowden N, Coupes B, Herrick A, Illingworth K, Jayson MI, Brenchley PE (1994) Plasma TGF β in systemic sclerosis: a cross-sectional study. Ann Rheum Dis 53:763–767
Higley H, Persichitte K, Chu S, Waegell W, Vancheeswaran R, Black C (1994) Immunocytochemical localization and serologic detection of transforming growth factor β1: association with type I procollagen and inflammatory cell markers in diffuse and limited systemic sclerosis, morphea, and Raynaud’s phenomenon. Arthritis Rheum 37:278–288
Falanga V, Julien JM (1990) Observations in the potential role of transforming growth factor- β in cutaneous fibrosis. Systemic sclerosis. Ann N Y Acad Sci 593:161–171
Giacomelli R, Cipriani P, Danese C, Pizzuto F, Lattanzio R, Parzanese I, et al (1996) Peripheral blood mononuclear cells of patients with systemic sclerosis produce increased amounts of interleukin 6, but not transforming growth factor β1. J Rheumatol 23:291–296
Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590
LeRoy EC, Krieg T, Black C, Medsger TAJ, Fleischmajer R, Rowell N, et al (1988) Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol 15:202–205
Sato S, Ihn H, Kikuchi K, Takehara K (1994) Antihistone antibodies in systemic sclerosis: association with pulmonary fibrosis. Arthritis Rheum 37:391–394
Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P, et al (1993) Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol 20:1892–1896
Gruschwitz M, Muller PU, Sepp N, Hofer E, Fontana A, Wick G (1990) Transcription and expression of transforming growth factor type β in the skin of progressive systemic sclerosis: a mediator of fibrosis? J Invest Dermatol 94:197–203
Kulozik M, Hogg A, Lankat-Buttgereit B, Krieg T (1990) Co-localization of Transforming growth factor β2 with α1(I) procollagen mRNA in tissue sections of patients with systemic sclerosis. J Clin Invest 86:917–922
Rossi P, Karsenty G, Roberts AB, Roche NS, Sporn MB, de Crombrugghe B (1988) A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor- β. Cell 52:405–414
Steen VD (1996) Organ involvement: renal. In: Clements PJ, Furst DE, (eds) Systemic sclerosis. Williams & Wilkins, Baltimore, pp 605–606
Ishikawa O, Ishikawa H (1992) Macrophage infiltration in the skin of patients with systemic sclerosis. J Rheumatol 19:1202–1206
Kraling BM, Maul GG, Jimenez SA (1995) Mononuclear cellular infiltrates in clinically involved skin from patients with systemic sclerosis of recent onset predominantly consist of monocytes/macrophages. Pathobiology 63:48–56
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The authors thank Ms. M. Matsubara and Ms. Y. Yamada for technical assistance.
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Hasegawa, M., Sato, S. & Takehara, K. Augmented production of transforming growth factor-β by cultured peripheral blood mononuclear cells from patients with systemic sclerosis. Arch Dermatol Res 296, 89–93 (2004). https://doi.org/10.1007/s00403-004-0472-5
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DOI: https://doi.org/10.1007/s00403-004-0472-5