Interferon-γ-inducible α-chemokine CXCL10 involvement in Graves' ophthalmopathy: Modulation by peroxisome proliferator-activated receptor-γ agonists

Alessandro Antonelli, Mario Rotondi, Silvia Martina Ferrari, Poupak Fallahi, Paola Romagnani, Stefano Sellari Franceschini, Mario Serio, Ele Ferrannini

Research output: Contribution to journalArticlepeer-review

Abstract

Context: CXC α-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-γ (IFNγ) and TNFα. Objective: Serum CXCL10 levels (sCXCL10) were measured in patients with active or inactive Graves' ophthalmopathy (GO). The effects of IFNγ and TNFα stimulation and peroxisome proliferator-activated receptor-γ (PPARγ) 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 TNFα alone, whereas stimulation with IFNγ or TNFα plus IFNγ induced CXCL10 release. Treatment of all cell types with the PPARγ agonist, rosiglitazone, dose-dependently (0.1-10 μM) suppressed IFNγ- plus TNFα-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. PPARγ activation plays an inhibitory role in this process.

Original languageEnglish
Pages (from-to)614-620
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number2
DOIs
Publication statusPublished - Feb 2006

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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