title: Peroxisome proliferator-activated receptor-α agonists modulate CXCL9 and CXCL11 chemokines in Graves' ophthalmopathy fibroblasts and preadipocytes.
abstract: Peroxisome proliferator-activated receptors (PPAR)α have been shown to exert immunomodulatory effects in autoimmune disorders; no study evaluated the effect of PPARα activation in Graves' ophthalmopathy (GO). We show the presence of PPARα, δ and γ in GO fibroblasts and preadipocytes. PPARα activators have a potent inhibitory action on the secretion of CXCL9 and CXCL11 chemokines (induced by IFNγ and TNFα) in fibroblasts and preadipocytes. The potency of the used PPARα 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. PPARα agonists were stronger inhibitors of CXCL9 and CXCL11 (in GO fibroblasts and preadipocytes) than PPARγ activators. This study first shows that PPARα activators inhibit CXCL9 and CXCL11 chemokines in normal and GO fibroblasts and preadipocytes, suggesting that PPARα may be involved in the modulation of the immune response in GO.
authors.affiliation: Department of Internal Medicine, University of Pisa - School of Medicine, Via Roma 67, I-56100 Pisa, Italy. alessandro.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: Ilaria
authors.initials: I
authors.lastname: Ruffilli
authors.forename: Stefania
authors.initials: S
authors.lastname: Gelmini
authors.forename: Michele
authors.initials: M
authors.lastname: Minuto
authors.forename: Cinzia
authors.initials: C
authors.lastname: Pupilli
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Sellari-Franceschini
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054371:Chemokine CXCL11 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D054370:Chemokine CXCL9 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005123:Eye / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011345:Fenofibrate / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049970:Graves Ophthalmopathy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011345:Fenofibrate