Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes
| Autor: | Michela Francalanci, Mariangela Sottili, Stefania Gelmini, Francesco Annunziato, Clara Crescioli, Veronica Santarlasci, Giuliano Perigli, Elisa Borgogni, Gabriella B. Vannelli, Lorenzo Cosmi, Erica Sarchielli, Anna Pezzatini, Mario Serio, Benedetta Mazzinghi |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Receptor expression Thyroid Gland Biology Rosiglitazone Interferon-gamma Endocrinology Antithyroid Agents Downregulation and upregulation Interferon Cell surface receptor Internal medicine medicine Humans CXCL10 Secretion Receptor Cells Cultured Methimazole Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha NF-kappa B Flow Cytometry Chemokine CXCL10 Depression Chemical Thiazolidinediones Tumor necrosis factor alpha Goiter Nodular medicine.drug |
| Zdroj: | Journal of Endocrinology. 195:145-155 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1677/joe-07-0240 |
| Popis: | 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)alpha demonstrates a potent synergistic effect on interferon (IFN)gamma-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFNgamma and TNFalpha and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferator-activated receptor gamma 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 IFNgamma membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kappaB (NF-kappaB). In human thyrocytes, the synergistic effect of TNFalpha with IFNgamma on CXCL10 secretion is due to the upregulation of IFNgamma receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNFalpha-induced upregulation of the IFNgamma receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kappaB translocation, without affecting IFNgamma 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. |
| Databáze: | OpenAIRE |
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