title: Interferon-α, -β and -γ induce CXCL11 secretion in human thyrocytes: modulation by peroxisome proliferator-activated receptor γ agonists.
abstract: It has been previously shown IFN-α, -β, -γ and TNF-α (synergically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 chemokines by thyroid follicular cells, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. No study has evaluated the effect of IFN-α and -β on CXCL11 chemokine production in thyrocytes. The aims of this study were: (a) to test the effect of IFN-α, -β and -γ on the secretion of the Th1 chemokine CXCL11, in primary cultures of human thyroid follicular cells; (b) to assess the effect of PPAR-γ activation on CXCL11 secretion. In primary cultures of human thyroid follicular cells, CXCL11 was undetectable in the supernatant. IFN-γ, -α and -β dose dependently induced CXCL11 release. TNF-α alone had no effect. The combination of each of the IFNs with TNF-α had a significant synergistic effect on CXCL11 secretion. Treatment of primary cultures of human thyroid follicular cells with rosiglitazone dose dependently inhibited the IFNs stimulated CXCL11 release. Compared with IFN-α and -β, IFN-γ was the most potent stimulus of CXCL11 secretion. In conclusion, we first show that IFN-α, -β and -γ and TNF-α (synergically with IFNs) dose-dependently induce the release of CXCL11 by primary cultures of human thyroid follicular cells, suggesting that this process may be related to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPAR-γ activation partially inhibits this process.
authors.affiliation: Department of Internal Medicine, University of Pisa, School of Medicine, Via Roma 67, 56100 Pisa, Italy. alessandro.antonelli@med.unipi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.forename: Silvia Martina
authors.initials: SM
authors.lastname: Ferrari
authors.forename: Caterina
authors.initials: C
authors.lastname: Mancusi
authors.forename: Valeria
authors.initials: V
authors.lastname: Mazzi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Pupilli
authors.forename: Marco
authors.initials: M
authors.lastname: Centanni
authors.forename: Clodoveo
authors.initials: C
authors.lastname: Ferri
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
mesh_terms: D054371:Chemokine CXCL11 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C515202:CXCL11 protein, human; D054371:Chemokine CXCL11; D007004:Hypoglycemic Agents; D016898:Interferon-alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D016899:Interferon-beta; D007371:Interferon-gamma