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 journalArticle

130 Citations (Scopus)

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

Fingerprint

Chemokine CXCL10
Graves Ophthalmopathy
Peroxisome Proliferator-Activated Receptors
Interferons
Modulation
rosiglitazone
Fibroblasts
Cell culture
Graves Disease
Chemical activation
CXC Chemokines
Serum
Chemokines
Cytokines
Thyroid Gland
Inflammation
Thyroid Epithelial Cells
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Interferon-γ-inducible α-chemokine CXCL10 involvement in Graves' ophthalmopathy : Modulation by peroxisome proliferator-activated receptor-γ agonists. / Antonelli, Alessandro; Rotondi, Mario; Ferrari, Silvia Martina; Fallahi, Poupak; Romagnani, Paola; Franceschini, Stefano Sellari; Serio, Mario; Ferrannini, Ele.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 2, 02.2006, p. 614-620.

Research output: Contribution to journalArticle

Antonelli, Alessandro ; Rotondi, Mario ; Ferrari, Silvia Martina ; Fallahi, Poupak ; Romagnani, Paola ; Franceschini, Stefano Sellari ; Serio, Mario ; Ferrannini, Ele. / Interferon-γ-inducible α-chemokine CXCL10 involvement in Graves' ophthalmopathy : Modulation by peroxisome proliferator-activated receptor-γ agonists. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 2. pp. 614-620.
@article{bd27e6be09c546f1bbda1ba00bcc6d6b,
title = "Interferon-γ-inducible α-chemokine CXCL10 involvement in Graves' ophthalmopathy: Modulation by peroxisome proliferator-activated receptor-γ agonists",
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.",
author = "Alessandro Antonelli and Mario Rotondi and Ferrari, {Silvia Martina} and Poupak Fallahi and Paola Romagnani and Franceschini, {Stefano Sellari} and Mario Serio and Ele Ferrannini",
year = "2006",
month = "2",
doi = "10.1210/jc.2005-1689",
language = "English",
volume = "91",
pages = "614--620",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - Interferon-γ-inducible α-chemokine CXCL10 involvement in Graves' ophthalmopathy

T2 - Modulation by peroxisome proliferator-activated receptor-γ agonists

AU - Antonelli, Alessandro

AU - Rotondi, Mario

AU - Ferrari, Silvia Martina

AU - Fallahi, Poupak

AU - Romagnani, Paola

AU - Franceschini, Stefano Sellari

AU - Serio, Mario

AU - Ferrannini, Ele

PY - 2006/2

Y1 - 2006/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=32544456285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32544456285&partnerID=8YFLogxK

U2 - 10.1210/jc.2005-1689

DO - 10.1210/jc.2005-1689

M3 - Article

C2 - 16303841

AN - SCOPUS:32544456285

VL - 91

SP - 614

EP - 620

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -