Systemic Sclerosis Fibroblasts Show Specific Alterations of Interferon-γ and Tumor Necrosis Factor-α-induced Modulation of Interleukin 6 and Chemokine Ligand 2

• Published in: Journal of rheumatology 2012-05, Vol.39 (5), p.979-985
• Main Authors: ANTONELLI, Alessandro, FALLAHI, Poupak, FERRARI, Silvia Martina, GIUGGIOLI, Dilia, COLACI, Michele, DOMENICANTONIO, Andrea Di, FERRI, Clodoveo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Cells, Cultured; Chemokine CCL2 - immunology; Chemokine CCL2 - metabolism; Chemokine CCL2 - secretion; Chemokine CXCL10 - immunology; Chemokine CXCL10 - metabolism; Chemokine CXCL10 - secretion; Diseases of the osteoarticular system; Female; Fibroblasts - drug effects; Fibroblasts - immunology; Fibroblasts - secretion; Humans; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Interleukin-6 - immunology; Interleukin-6 - metabolism; Interleukin-6 - secretion; Male; Medical sciences; Middle Aged; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma, Systemic - immunology; Scleroderma, Systemic - metabolism; Scleroderma, Systemic - pathology; Th1 Cells - immunology; Th1 Cells - metabolism; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.111132

We evaluated the effect of interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) on the secretion of prototype proinflammatory cytokine interleukin 6 (IL-6), compared to T-helper 1 [Th1; chemokine (C-X-C motif) ligand 10 (CXCL10)] or Th2 [chemokine (C-C motif) ligand 2 (CCL2)] chemokines, in primary cultured fibroblasts from patients with systemic sclerosis (SSc) at an early stage of the disease. Fibroblast cultures from 5 SSc patients (disease duration < 2 yrs) and 5 healthy controls were evaluated for the production of IL-6, CXCL10, and CCL2 at the basal level and after stimulation with IFN-γ and/or TNF-α. SSc fibroblasts basally produced higher levels of IL-6 than controls, while no difference was observed about CCL2 and CXCL10. TNF-α was able to dose-dependently induce IL-6 and CCL2 secretion in SSc, but not in control fibroblasts. By stimulation with increasing doses of IFN-γ, SSc fibroblasts were induced to secrete CCL2 and CXCL10, while no effect was observed on IL-6. The combination of IFN-γ and TNF-α induced a strong secretion of IL-6 and CCL2 in SSc fibroblasts but not in controls. In contrast, the synergistic effect of IFN-γ and TNF-α on CXCL10 secretion was similar in SSc fibroblasts and in controls. SSc fibroblasts participate in the self-perpetuation of inflammation by releasing IL-6, CXCL10, and CCL2 under the influence of IFN-γ and/or TNF-α. SSc fibroblasts are more active than controls in the secretion of IL-6 at baseline, and in the production of IL-6 and CCL2 under the combined IFN-γ/TNF-α stimulation.