Cytokine production and serum levels in systemic sclerosis

Kantor, Thomas V.; Friberg, Diana; Medsger, Thomas A.; Buckingham, Robert B.; Whiteside, Theresa L.

doi:10.1016/0090-1229(92)90158-k

Cited by 59 publications

(40 citation statements)

References 18 publications

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“…might also occur in scleroderma patients. Until now, it was believed that the increase in the serum concentration of TNF reflected the inflammatory stages and also the extent of internal involvement (23,24). The results of this study suggest that it may in fact function to improve the clinical condition.…”

Section: Discussionmentioning

confidence: 55%

Disruption of tumor necrosis factor receptor p55 impairs collagen turnover in experimentally induced sclerodermic skin fibroblasts

Murota¹,

Hamasaki²,

Nakashima³

et al. 2003

Arthritis & Rheumatism

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Objective. To determine the role of tumor necrosis factor receptor p55 (TNFRp55)-mediated signaling in the pathogenesis of scleroderma.Methods. A murine model of scleroderma that closely resembles systemic sclerosis in humans was used. Wild-type and TNFRp55-deficient (TNFRp55 ؊/؊ ) mice received a subcutaneous injection of bleomycin each day. The extent of skin fibrosis was determined by measurements of the dermal thickness, as well as histologic examinations. Expression levels of fibrogenic cytokines, procollagen ␣1, and matrix metalloproteinase 1 (MMP-1), MMP-2, and MMP-9 messenger RNA (mRNA) were analyzed, both in vivo and in vitro, by reverse transcriptase-polymerase chain reaction assay or Western blotting.Results. TNFRp55 ؊/؊ mice began to develop severe sclerotic changes of the dermis on day 3 of the subcutaneous injections of bleomycin, while wild-type mice did not. The expression levels of fibrogenic cytokines, procollagen ␣1, and MMP-2 and MMP-9 mRNA were unaffected in the skin of both wild-type and TNFRp55 ؊/؊ mice, with or without bleomycin treatment. Induction of MMP-1 expression was significantly inhibited in the skin from bleomycin-treated TNFRp55 ؊/؊ mice, and this phenomenon was also observed in vitro.Conclusion. These results indicated that signaling mediated by TNFRp55 plays an essential role in MMP-1 expression and a key role in the collagen degradation process in this murine model. This study might provide a basis for understanding the pathogenesis of scleroderma and formulating therapeutic intervention.

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Section: Discussionmentioning

confidence: 55%

Disruption of tumor necrosis factor receptor p55 impairs collagen turnover in experimentally induced sclerodermic skin fibroblasts

Murota¹,

Hamasaki²,

Nakashima³

et al. 2003

Arthritis & Rheumatism

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“…Endothelial cell activation is evident, as suggested by the expression of E-selectin (18)(19)(20), TGF␤ (21), and endothelin 1 (22,23). Monocyte activation is also reported, as documented by increased production in the peripheral blood of superoxide anion (24), , IL-1, and TGF␤ (26). Other cells that are found to be activated in SSc include eosinophils (27), mast cells (18), and T cells (28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

“…MMP ϭ matrix metalloproteinase. phages (26,41,96). IL-1 induces production of collagen, IL-6, and PDGF by fibroblasts and endothelial cells (96).…”

Section: T Cell Activation and Cytokine Production In Ssc Leading To mentioning

confidence: 99%

Is systemic sclerosis an antigen‐driven T cell disease?

Sakkas¹,

Platsoucas²

2004

Arthritis & Rheumatism

113

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“…Several cytokines which contribute to the worsening of the disease have been found in the sera and BALF of patients with active scleroderma [6][7][8]. The studies of cytokines produced in vitro by peripheral blood mononuclear cells (PBMC) in SSc patients showed a spontaneous release of the 'fibrogenetic' cytokines tumour necrosis factor-alpha (TNF-a) and IL-1b, and an impairment of mitogen-induced IFN-g production [9,10]. In particular, the production of IFN-g is of great relevance: it is the most potent stimulator of HLA class II antigens on endothelial cells, thus up-regulating endothelial-leucocyte adhesion [11][12][13], but it is also a negative regulator of collagen production by fibroblasts [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon

Molteni

Bella

Mascagni

et al. 1999

Clinical and Experimental Immunology

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SUMMARYThe aim of the present study was to analyse the in vitro proliferation and cytokine production by alloantigen-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC stimulated in vitro with alloantigens was significantly increased compared with healthy subjects, while no differences were observed for RP patients. Lymphocytes from SSc patients also produced larger amounts of IFN-g compared with healthy controls. However, patients with clinically active disease had lower IFN-g levels than those found in clinically stable patients. Patients affected by RP showed significantly higher levels of IFN-g than healthy subjects. Analysis at the clonal level of the lymphocyte subsets involved in alloantigen stimulation in one patient affected by active SSc, and one subject with RP confirmed the results obtained using PBMC. In particular, in the RP patient but not in the SSc patient, we observed a population of CD4 þ T cells which proliferated to alloantigens in vitro and produced high levels of IFN-g. We suggest that T lymphocytes producing high levels of IFN-g might play a protective role in RP patients and in established scleroderma.

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Cytokine production and serum levels in systemic sclerosis

Cited by 59 publications

References 18 publications

Disruption of tumor necrosis factor receptor p55 impairs collagen turnover in experimentally induced sclerodermic skin fibroblasts

Disruption of tumor necrosis factor receptor p55 impairs collagen turnover in experimentally induced sclerodermic skin fibroblasts

Is systemic sclerosis an antigen‐driven T cell disease?

Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon

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