This Article Full Text Full Text (PDF) All Versions of this Article: 91/2/614    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Antonelli, A. Articles by Ferrannini, E. Search for Related Content PubMed PubMed Citation Articles by Antonelli, A. Articles by Ferrannini, E. Related Collections Thyroid

Interferon--Inducible -Chemokine CXCL10 Involvement in Graves’ Ophthalmopathy: Modulation by Peroxisome Proliferator-Activated Receptor- Agonists

Department of Medicine (A.A., S.M.F., P.F., E.F.) and Otorhinolaryngology Unit (S.S.F.), University of Pisa School of Medicine, I-56100 Pisa, Italy; Department of Clinical and Experimental Medicine and Surgery F. Magrassi–A. Lanzara, Second University of Naples (M.R.), 80100 Naples, Italy; and Department of Clinical Pathophysiology, Endocrinology Unit, University of Florence (P.R., M.S.), 50100 Florence, Italy

Address all correspondence and requests for reprints to: Dr. Alessandro Antonelli, Department of Internal Medicine, University of Pisa School of Medicine, Via Roma 67, I-56100 Pisa, Italy. E-mail: a.antonelli{at}med.unipi.it.

Context: CXC -chemokine CXCL10/inducing protein-10 play an important role in the initial phases of autoimmune thyroid disorders. Human thyrocytes in primary culture produce large amounts of CXCL10 when stimulated by interferon- (IFN) and TNF.

Objective: Serum CXCL10 levels (sCXCL10) were measured in patients with active or inactive Graves’ ophthalmopathy (GO). The effects of IFN and TNF stimulation and peroxisome proliferator-activated receptor- (PPAR) activation on CXCL10 secretion in primary cultures of thyrocytes, orbital fibroblasts, and preadipocytes were tested.

Patients: Sixty consecutive patients with Graves’ disease, 60 age- and sex-matched patients with GO, and 60 controls were studied.

Results: sCXCL10 was higher (P < 0.0001) in Graves’ disease (120 ± 83 pg/ml; n = 60) and GO (122 ± 71; n = 60) patients than in age- and sex-matched euthyroid controls (72 ± 32; n = 60). Among GO patients, sCXCL10 levels were significantly higher in those (n = 14) with active disease (171 ± 197) than in those with inactive disease (114 ± 45 pg/ml; P < 0.003). In primary cultures of thyrocytes, retrobulbar fibroblasts and retrobulbar preadipocytes from GO patients, CXCL10 production was absent under basal conditions; dose-dependent secretion of CXCL10 was not induced by TNF alone, whereas stimulation with IFN or TNF plus IFN induced CXCL10 release. Treatment of all cell types with the PPAR agonist, rosiglitazone, dose-dependently (0.1–10 µM) suppressed IFN- plus TNF-induced CXCL10 release.

Conclusions: We conclude that in GO, thyrocytes and retrobulbar cell types participate in the self-perpetuation of inflammation by releasing chemokines under the influence of cytokines. PPAR activation plays an inhibitory role in this process.

This article has been cited by other articles:

				A. Antonelli, S. M. Ferrari, P. Fallahi, P. Berti, G. Materazzi, I. Marchetti, C. Ugolini, F. Basolo, P. Miccoli, and E. Ferrannini Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration Eur. J. Endocrinol., September 1, 2008; 159(3): 283 - 291. [Abstract] [Full Text] [PDF]

				E. Borgogni, E. Sarchielli, M. Sottili, V. Santarlasci, L. Cosmi, S. Gelmini, A. Lombardi, G. Cantini, G. Perigli, M. Luconi, et al. Elocalcitol Inhibits Inflammatory Responses in Human Thyroid Cells and T Cells Endocrinology, July 1, 2008; 149(7): 3626 - 3634. [Abstract] [Full Text] [PDF]

				A. Antonelli, C. Ferri, P. Fallahi, S. M. Ferrari, D. Giuggioli, M. Colaci, A. Manfredi, S. Frascerra, F. Franzoni, F. Galetta, et al. CXCL10 ({alpha}) and CCL2 ( ) chemokines in systemic sclerosis a longitudinal study Rheumatology, January 1, 2008; 47(1): 45 - 49. [Abstract] [Full Text] [PDF]

				C Crescioli, L Cosmi, E Borgogni, V Santarlasci, S Gelmini, M Sottili, E Sarchielli, B Mazzinghi, M Francalanci, A Pezzatini, et al. Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes J. Endocrinol., October 1, 2007; 195(1): 145 - 155. [Abstract] [Full Text] [PDF]

				M. Rotondi, L. Chiovato, S. Romagnani, M. Serio, and P. Romagnani Role of Chemokines in Endocrine Autoimmune Diseases Endocr. Rev., August 1, 2007; 28(5): 492 - 520. [Abstract] [Full Text] [PDF]

				Y. Inukai, A. Momobayashi, N. Sugawara, and Y. Aso Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves' disease Eur. J. Endocrinol., June 1, 2007; 156(6): 623 - 630. [Abstract] [Full Text] [PDF]

				A. Antonelli, C. Ferri, P. Fallahi, M. Cazzato, S. M. Ferrari, M. Sebastiani, and E. Ferrannini Clinical and subclinical autoimmune thyroid disorders in systemic sclerosis Eur. J. Endocrinol., April 1, 2007; 156(4): 431 - 437. [Abstract] [Full Text] [PDF]

				A. Antonelli, P. Fazzi, P. Fallahi, S. M. Ferrari, and E. Ferrannini Prevalence of hypothyroidism and graves disease in sarcoidosis. Chest, August 1, 2006; 130(2): 526 - 532. [Abstract] [Full Text] [PDF]