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¹ Departments of Clinical Pathophysiology,
² Internal Medicine, Center for Research Transfer and High Education ‘DENOthe’,
³ General Surgery Medical School and
⁴ Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy

(Correspondence should be addressed to C Crescioli who is now at Unit of Endocrinology, Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy; Email: c.crescioli{at}dfc.unifi.it)

CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the self-perpetuation of the inflammatory processes in patients with autoimmune thyroid disease. Treatment with methimazole (MMI) reduces serum CXCL10 in patients with Graves’ disease. In isolated human thyrocytes, tumor necrosis factor (TNF) demonstrates a potent synergistic effect on interferon (IFN)-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFN and TNF and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferator-activated receptor agonist, rosiglitazone (RGZ), a known inhibitor of T helper 1 (Th1)-mediated responses, was also studied for comparison. Experiments were carried out in human thyrocytes isolated from internodular parenchyma of thyroid tissues derived from patients who had undergone surgery for multinodular goiter. ELISA was used to measure CXCL10 levels in culture supernatant. Flow cytometry was used to assess IFN membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-B (NF-B). In human thyrocytes, the synergistic effect of TNF with IFN on CXCL10 secretion is due to the upregulation of IFN receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNF-induced upregulation of the IFN receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-B translocation, without affecting IFN receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper 1-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.

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