title: Cytokines differentially regulate CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated human gingival fibroblasts.
abstract: OBJECTIVE
  CXC chemokine 10 (CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T-helper 1 cells. In this study we examined the effects of cytokines on CXCL10 production by human gingival fibroblasts.
  
  
  METHODS
  Human gingival fibroblasts were exposed to pro-inflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha), a T-helper 1 cytokine (interferon-gamma), T-helper 2 cytokines (interleukin-4, interleukin-13), T-helper 17 cytokines (interleukin-17A, interleukin-22) and regulatory T-cell cytokines (interleukin-10, transforming growth factor-beta1) for 24 h. CXCL10 production by human gingival fibroblasts was examined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Human gingival fibroblasts produced CXCL10 protein upon stimulation with interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma. Treatment of human gingival fibroblasts with interferon-gamma in combination with tumor necrosis factor-alpha or interleukin-1beta resulted in a synergistic production of CXCL10. However, interleukin-4 and interleukin-13 inhibited CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated-human gingival fibroblasts. On the other hand, interleukin-17A and interleukin-22 enhanced CXCL10 production by human gingival fibroblasts treated with interferon-gamma and inhibited CXCL10 production by tumor necrosis factor-alpha-stimulated human gingival fibroblasts. Furthermore, the anti-inflammatory cytokine, interleukin-10, inhibited CXCL10 production by both interferon-gamma- and tumor necrosis factor-alpha-stimulated human gingival fibroblasts, but transforming growth factor-beta1 enhanced interferon-gamma-mediated CXCL10 production by human gingival fibroblasts.
  
  
  CONCLUSIONS
  These results mean that the balance of cytokines in periodontally diseased tissue may be essential for the control of CXCL10 production by human gingival fibroblasts, and the production of CXCL10 might be important for the regulation of T-helper 1 cell infiltration in periodontally diseased tissue.
authors.affiliation: Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: I
authors.initials: I
authors.lastname: Hosokawa
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Nakae
authors.forename: T
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054357:Chemokine CXCL10; D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma