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Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

Journal Article · · Experimental Cell Research
 [1];  [1];  [1];  [2];  [1];  [3];  [1];  [1]
  1. Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)
  2. Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy)
  3. Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy)

Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} 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 PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

OSTI ID:
22212149
Journal Information:
Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 11 Vol. 317; ISSN 0014-4827; ISSN ECREAL
Country of Publication:
United States
Language:
English

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