title: Systemic sclerosis fibroblasts show specific alterations of interferon-γ and tumor necrosis factor-α-induced modulation of interleukin 6 and chemokine ligand 2.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Metabolism Unit, University of Pisa School of Medicine, Pisa, Italy. alessandro.antonelli@med.unipi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
authors.forename: Silvia Martina
authors.initials: SM
authors.lastname: Ferrari
authors.forename: Dilia
authors.initials: D
authors.lastname: Giuggioli
authors.forename: Michele
authors.initials: M
authors.lastname: Colaci
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Domenicantonio
authors.forename: Clodoveo
authors.initials: C
authors.lastname: Ferri
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma