title: Extra-ocular muscle cells from patients with Graves' ophthalmopathy secrete α (CXCL10) and β (CCL2) chemokines under the influence of cytokines that are modulated by PPARγ.
abstract: To our knowledge, no study has evaluated the involvement of T helper (Th)1- and Th2-chemokines in extra-ocular muscle (EOM) myopathy in "patients with thyroid-associated ophthalmopathy" (TAO-p). We tested the effects of interferon (IFN)γ and tumor necrosis factor (TNF)α stimulation, and of increasing concentrations of peroxisome proliferator-activated receptor (PPAR)γ agonists (pioglitazone or rosiglitazone; 0.1 μM-20 μM), on Th1-chemokine [C-X-C motif ligand (CXCL)10] and Th2-chemokine [C-C motif ligand (CCL)2] secretion in primary EOM cultures from TAO-p vs. control myoblasts. Moreover, we evaluated serum CXCL10 and CCL2 in active TAO-p with prevalent EOM involvement (EOM-p) vs. those with prevalent orbital fat expansion (OF-p). Serum CXCL10 was higher in OF-p and EOM-p vs. controls, while serum CCL2 was not significantly different in controls, or in OF-p and EOM-p. We showed the expression of PPARγ in EOM cells. In primary EOM cultures from TAO-p: a) CXCL10 was undetectable in the supernatant, IFNγ dose-dependently induced it, whereas TNFα did not; b) EOM produced basally low amounts of CCL2, TNFα dose-dependently induced it, whereas IFNγ did not; c) the combination of TNFα and IFNγ had a significant synergistic effect on CXCL10 and CCL2 secretion; and d) PPARγ agonists have an inhibitory role on the modulation of CXCL10, while they stimulate CCL2 secretion. EOM participates in the self-perpetuation of inflammation by releasing both Th1 (CXCL10) and Th2 (CCL2) chemokines under the influence of cytokines, in TAO. PPARγ agonist activation plays an inhibitory role on CXCL10, but stimulates the release of CCL2.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: alessandro.antonelli@med.unipi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: sm.ferrari@int.med.unipi.it.
authors.forename: Silvia Martina
authors.initials: SM
authors.lastname: Ferrari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: corradoalda@gmail.com.
authors.forename: Alda
authors.initials: A
authors.lastname: Corrado
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: s.sellari@ent.med.unipi.it.
authors.forename: Stefano Sellari
authors.initials: SS
authors.lastname: Franceschini
authors.affiliation: Clinical Biochemistry Unit, Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. Electronic address: s.gelmini@dfc.unifi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gelmini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: ferranni@ifc.cnr.it.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: poupak@int.med.unipi.it.
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
mesh_terms: D018932:Chemokine CCL2 / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism*; D049970:Graves Ophthalmopathy / Q000276:immunology*; D006801:Humans; D018482:Muscle, Skeletal / Q000276:immunology* / Q000378:metabolism; D032446:Myoblasts / Q000276:immunology / Q000378:metabolism; D047495:PPAR gamma / Q000276:immunology*
chemical_list: C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D047495:PPAR gamma
keywords: CCL2; CXCL10; Chemokines; Extra-ocular muscles; Graves' ophthalmopathy