title: Interferon-γ and tumor necrosis factor-α sustain secretion of specific CXC chemokines in human thyrocytes: a first step toward a differentiation between autoimmune and tumor-related inflammation?
abstract: BACKGROUND
  Chemokines are chemotactic cytokines responsible for the attraction and recruitment of different cell types during leukocyte infiltration, the histopathological hallmark of autoimmunity. Previous data demonstrate that thyrocytes secrete CXC chemokines, particularly CXCL8 and CXCL10. However, the physiopathological significance of such secretion and the effects of a combination of proinflammatory stimuli in terms of preferential CXCL8 and CXCL10 release remain unclear.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether the secretion of chemokines by human thyrocytes is a generalized inflammatory response or whether it is dependent upon specific proinflammatory stimuli.
  
  
  METHODS
  CXCL8 and CXCL10 were measured in supernatants of human thyrocytes in primary cultures basally and after 24 h stimulation with interferon-γ (IFNγ) (1000 U/ml) and TNFα (10 ng/ml), alone or in combination.
  
  
  RESULTS
  CXCL8 but not CXCL10 was detected in basal conditions. The two chemokines showed differences in their response to proinflammatory cytokines. Indeed, significant secretion of CXCL10 was induced by IFNγ (P < 0.01) and not TNFα, whereas CXCL8 was secreted in response to TNFα (P < 0.01) being inhibited by IFNγ (P < 0.01). The combination of TNFα plus IFNγ synergistically increased the IFNγ-induced CXCL10 secretion (P < 0.01) and reversed the TNFα-induced CXCL8 secretion (P < 0.01).
  
  
  CONCLUSIONS
  These results confirm that human thyrocytes secrete CXC chemokines and demonstrate that the secretion of CXCL8 and CXCL10 is sustained by specific proinflammatory cytokines or their combination, which ultimately determines the nature of the infiltrating lymphocytes in human thyroid diseases. These results indirectly support a major role for CXCL10 in thyroid autoimmunity whereas CXCL8 might be involved in tumor-related inflammation.
authors.affiliation: Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, University of Pavia, Via S. Maugeri 10, I-27100, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.forename: Francesca
authors.initials: F
authors.lastname: Coperchini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pignatti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sideri
authors.forename: Gloria
authors.initials: G
authors.lastname: Groppelli
authors.forename: Paola
authors.initials: P
authors.lastname: Leporati
authors.forename: Luigi
authors.initials: L
authors.lastname: La Manna
authors.forename: Flavia
authors.initials: F
authors.lastname: Magri
authors.forename: Stefano
authors.initials: S
authors.lastname: Mariotti
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D002277:Carcinoma / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism / Q000502:physiology; D019743:Chemokines, CXC / Q000378:metabolism*; D003937:Diagnosis, Differential; D004353:Drug Evaluation, Preclinical; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D013966:Thyroiditis / Q000175:diagnosis / Q000209:etiology*; D013967:Thyroiditis, Autoimmune / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma