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

Context: Peroxisome proliferator-activated receptor (PPAR)-alpha has been shown to exert immunomodulatory effects in autoimmune disorders. However, until now, no data were present in the literature about the effect of PPAR alpha activation on CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in thyroid cells. Objective and Design: The presence of PPAR alpha and PPAR gamma has been evaluated by real-time-PCR in Graves' disease (GD) and control cells in primary culture. Furthermore, we have tested the role of PPAR alpha and PPAR gamma activation on CXCL9 and CXCL11 secretion in GD and control cells after stimulation of these chemokines secretion with IFN gamma and TNF alpha. Results: This study shows the presence of PPAR alpha and PPAR gamma in GD and control cells. A potent dose-dependent inhibition by PPAR alpha-agonists was observed on the cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The potency of the PPAR alpha 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). PPAR alpha agonists were stronger (ANOVA, P < 0.001) inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPAR gamma agonists. Conclusions: Our study shows the presence of PPAR alpha in GD and control thyrocytes. PPAR alpha activators are potent inhibitors of the secretion of CXCL9 and CXCL11, suggesting that PPAR alpha may be involved in the modulation of the immune response in the thyroid. (J Clin Endocrinol Metab 95: E413-E420, 2010)