Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

被引:54
作者
Crescioli, C.
Cosmi, L.
Borgogni, E.
Santarlasci, V.
Gelmini, S.
Sottili, M.
Sarchielli, E.
Mazzinghi, B.
Francalanci, M.
Pezzatini, A.
Perigli, G.
Vannelli, G. B.
Annunziato, F.
Serio, M.
机构
[1] Univ Florence, Dept Clin Pathophysiol, Unit Endocrinol, I-50139 Florence, Italy
[2] Univ Florence, Dept Anat Histol & Forens Med, Florence, Italy
[3] Univ Florence, Gen Surg Med Sch, Florence, Italy
[4] Univ Florence, Ctr Res Transfer & High Educ DENOthe, Dept Internal Med, Florence, Italy
关键词
D O I
10.1677/JOE-07-0240
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 IFN gamma and TNF alpha 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 front 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 gamma membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kappa B (NF-kappa B). In human thyrocytes, the synergistic effect of TNF alpha with IFN gamma on CXCL10 secretion is due to the upregulation of IFN gamma receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNF alpha-induced upregulation of the IFN gamma receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kappa B translocation, without affecting IFN gamma receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper I-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.
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页码:145 / 155
页数:11
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