title: Peroxisome proliferator-activated receptor α agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease.
abstract: Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR)α activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPARα and PPARγ activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN)γ and tumor necrosis factor (TNF)α. IFNγ stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNFα alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFNγ and TNFα had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPARα activators inhibited the secretion of both chemokines (stimulated with IFNγ and TNFα) at a level higher (for CXCL10, about 60-72%) than PPARγ agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFNγ and TNFα in GD and normal thyrocytes. Furthermore we first show that PPARα activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.
authors.affiliation: Department of Internal Medicine, University of Pisa-School of Medicine, Pisa, Italy. a.antonelli@med.unipi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.forename: Silvia Martina
authors.initials: SM
authors.lastname: Ferrari
authors.forename: Silvia
authors.initials: S
authors.lastname: Frascerra
authors.forename: Alda
authors.initials: A
authors.lastname: Corrado
authors.forename: Cinzia
authors.initials: C
authors.lastname: Pupilli
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bernini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Benvenga
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D011345:Fenofibrate / Q000494:pharmacology; D058607:Fibric Acids / Q000494:pharmacology; D006111:Graves Disease / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists*; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C019304:ciprofibrate; D011345:Fenofibrate