title: CXCL9 and CXCL11 chemokines modulation by peroxisome proliferator-activated receptor-alpha agonists secretion in Graves' and normal thyrocytes.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor (PPAR)-α has been shown to exert immunomodulatory effects in autoimmune disorders. However, until now, no data were present in the literature about the effect of PPARα activation on CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in thyroid cells.
  
  
  OBJECTIVE
  The presence of PPARα and PPARγ has been evaluated by real-time-PCR in Graves' disease (GD) and control cells in primary culture. Furthermore, we have tested the role of PPARα and PPARγ activation on CXCL9 and CXCL11 secretion in GD and control cells after stimulation of these chemokines secretion with IFNγ and TNFα.
  
  
  RESULTS
  This study shows the presence of PPARα and PPARγ in GD and control cells. A potent dose-dependent inhibition by PPARα-agonists was observed on the cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The potency of the PPARα agonists used was maximum on the secretion of CXCL9, reaching about 90% of inhibition by fenofibrate and 85% by ciprofibrate. The relative potency of the compounds was different with each chemokine; for example, gemfibrozil exerted a 55% inhibition on CXCL11, whereas it had a weaker activity on CXCL9 (40% inhibition). PPARα agonists were stronger (ANOVA, P<0.001) inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPARγ agonists.
  
  
  CONCLUSIONS
  Our study shows the presence of PPARα in GD and control thyrocytes. PPARα activators are potent inhibitors of the secretion of CXCL9 and CXCL11, 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, Via Roma, 67, I-56100, 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: Cinzia
authors.initials: C
authors.lastname: Pupilli
authors.forename: Caterina
authors.initials: C
authors.lastname: Mancusi
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Metelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Orlando
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
mesh_terms: D000328:Adult; D054371:Chemokine CXCL11 / Q000187:drug effects / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology; D015248:Gemfibrozil / Q000494:pharmacology; D006111:Graves Disease / Q000276:immunology / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists* / Q000494:pharmacology / Q000502:physiology; D047495:PPAR gamma / Q000494:pharmacology / Q000502:physiology; D000077205:Pioglitazone; D013601:T-Lymphocytes / Q000276:immunology; D045162:Thiazolidinediones / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D013965:Thyroidectomy
chemical_list: D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D016207:Cytokines; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D007371:Interferon-gamma; D015248:Gemfibrozil; D011345:Fenofibrate; D000077205:Pioglitazone