Peroxisome proliferator-activated receptor-α agonists modulate CXCL9 and CXCL11 chemokines in Graves' ophthalmopathy fibroblasts and preadipocytes

被引：21

作者：

Antonelli, Alessandro ^{[1
]}

Ferrari, Silvia Martina ^{[1
]}

Frascerra, Silvia ^{[1
]}

Ruffilli, Ilaria ^{[1
]}

Gelmini, Stefania ^{[2
]}

Minuto, Michele ^{[3
]}

Pupilli, Cinzia ^{[4
,5
]}

Miccoli, Paolo ^{[3
]}

Sellari-Franceschini, Stefano ^{[6
]}

Ferrannini, Ele ^{[1
]}

Fallahi, Poupak ^{[1
]}

机构：

[1] Univ Pisa, Sch Med, Dept Internal Med, I-56100 Pisa, Italy

[2] Univ Florence, Dept Clin Pathophysiol, Clin Biochem Unit, I-50139 Florence, Italy

[3] Univ Pisa, Dept Surg, I-56124 Pisa, Italy

[4] Azienda Osped Careggi, Endocrinol Unit, I-50134 Florence, Italy

[5] Univ Florence, I-50134 Florence, Italy

[6] Univ Pisa, Dept Otorhinolaryngol, I-56100 Pisa, Italy

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2012年 / 349卷 / 02期

关键词：

Graves' ophthalmopathy; CXCL9; CXCL11; PPAR alpha; Fibroblasts; Cytokines; HUMAN ENDOTHELIAL-CELLS; NF-KAPPA-B; GAMMA AGONISTS; PPAR-GAMMA; GENE-EXPRESSION; AUTOIMMUNE-THYROIDITIS; DISEASE; HYPOTHYROIDISM; ROSIGLITAZONE; PIOGLITAZONE;

D O I：

10.1016/j.mce.2011.11.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Peroxisome proliferator-activated receptors (PPAR)alpha have been shown to exert immunomodulatory effects in autoimmune disorders: no study evaluated the effect of PPAR alpha activation in Graves' ophthalmopathy (GO). We show the presence of PPAR alpha, delta and gamma in GO fibroblasts and preadipocytes. PPAR alpha activators have a potent inhibitory action on the secretion of CXCL9 and CXCL11 chemokines (induced by IFN gamma and TNF alpha) in fibroblasts and preadipocytes. The potency of the used PPAR alpha agonists was maximum on the secretion of CXCL11 (67% inhibition by fenofibrate) in fibroblasts. The relative potency of the compounds in GO fibroblasts was different with each chemokine. PPAR alpha agonists were stronger inhibitors of CXCL9 and CXCL11 (in GO fibroblasts and preadipocytes) than PPAR gamma activators. This study first shows that PPAR alpha activators inhibit CXCL9 and CXCL11 chemokines in normal and GO fibroblasts and preadipocytes, suggesting that PPAR alpha may be involved in the modulation of the immune response in GO. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：255 / 261

页数：7

共 35 条

[1]

Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper- or hypothyroidism per se, but is specifically sustained by the autoimmune, inflammatory process [J].

Antonelli, A ;

Fallahi, P ;

Rotondi, M ;

Ferrari, SM ;

Romagnani, P ;

Grosso, M ;

Ferrannini, E ;

Serio, M .

EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2006, 154 (05) :651-658

[2]

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

Antonelli, A ;

Rotondi, M ;

Ferrari, SM ;

Fallahi, P ;

Romagnani, P ;

Franceschini, SS ;

Serio, M ;

Ferrannini, E .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (02) :614-620

[3]

High levels of circulating CXC chemokine ligand 10 are associated with chronic autoimmune thyroiditis and hypothyroidism [J].

Antonelli, A ;

Rotondi, M ;

Fallahi, P ;

Romagnani, P ;

Ferrari, SM ;

Buonamano, A ;

Ferrannini, E ;

Serio, M .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (11) :5496-5499

[4]

Iodine-131 given for therapeutic purposes modulates differently interferon-γ-inducible α-chemokine CXCL10 serum levels in patients with active Graves' disease or toxic nodular goiter [J].

Antonelli, Alessandro ;

Rotondi, Mario ;

Fallahi, Poupak ;

Grosso, Mariano ;

Boni, Giuseppe ;

Ferrari, Silvia Martina ;

Romagnani, Paola ;

Serio, Mario ;

Mariani, Giuliano ;

Ferrannini, Ele .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (04) :1485-1490

[5]

CXCL9 and CXCL11 Chemokines Modulation by Peroxisome Proliferator-Activated Receptor-α Agonists Secretion in Graves' and Normal Thyrocytes [J].

Antonelli, Alessandro ;

Ferrari, Silvia Martina ;

Frascerra, Silvia ;

Pupilli, Cinzia ;

Mancusi, Caterina ;

Metelli, Maria Rita ;

Orlando, Claudio ;

Ferrannini, Ele ;

Fallahi, Poupak .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2010, 95 (12) :E413-E420

[6]

Cytokines (interferon-γ and tumor necrosis factor-α)-induced nuclear factor-κB activation and chemokine (C-X-C motif) ligand 10 release in Graves disease and ophthalmopathy are modulated by pioglitazone [J].

Antonelli, Alessandro ;

Ferrari, Silvia Martina ;

Fallahi, Poupak ;

Piaggi, Simona ;

Paolicchi, Aldo ;

Franceschini, Stefano Sellari ;

Salvi, Mario ;

Ferrannini, Ele .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2011, 60 (02) :277-283

[7]

Monokine Induced by Interferon γ(IFNγ) (CXCL9) and IFNγ Inducible T-Cell α-Chemoattractant (CXCL11) Involvement in Graves' Disease and Ophthalmopathy: Modulation by Peroxisome Proliferator-Activated Receptor-γ Agonists [J].

Antonelli, Alessandro ;

Ferrari, Silvia Martina ;

Fallahi, Poupak ;

Frascerra, Silvia ;

Santini, Eleonora ;

Franceschini, Stefano Sellari ;

Ferrannini, Ele .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (05) :1803-1809

[8]

PRESENCE OF ANTIBODIES IN THE SERA OF PATIENTS WITH GRAVES-DISEASE RECOGNIZING A 23 KILODALTON FIBROBLAST PROTEIN [J].

BAHN, RS ;

GORMAN, CA ;

JOHNSON, CM ;

SMITH, TJ .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1989, 69 (03) :622-628

[9]

PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation [J].

Chawla, A ;

Barak, Y ;

Nagy, L ;

Liao, D ;

Tontonoz, P ;

Evans, RM .

NATURE MEDICINE, 2001, 7 (01) :48-52

[10]

Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors [J].

Cunard, R ;

Ricote, M ;

DiCampli, D ;

Archer, DC ;

Kahn, DA ;

Glass, CK ;

Kelly, CJ .

JOURNAL OF IMMUNOLOGY, 2002, 168 (06) :2795-2802

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