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A Antonelli, Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
S Ferrari, Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
P Fallahi, Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
S Frascerra, Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
S Piaggi, Department of Experimental Pathology, University of Pisa, Pisa, Italy
S Gelmini, Clinical Biochemistry Unit, Department of Clinical Pathophysiology, University of Florence, Firenze, Italy
C Lupi, Department of Surgery, Pathology Unit, University of Pisa, Pisa, Italy
M Minuto, Department of Surgery, University of Pisa, Pisa, Italy
P Berti, Department of Surgery, University of Pisa, Pisa, Italy
S Benvenga, Department of Endocrinology, University of Messina, Messina, Italy
F Basolo, Department of Surgery, Pathology Unit, University of Pisa, Pisa, Italy
C Orlando, Clinical Biochemistry Unit, Department of Clinical Pathophysiology, University of Florence, Firenze, Italy
P Miccoli, Department of Surgery, University of Pisa, Pisa, Italy

Alessandro Antonelli, Email: a.antonelli{at}med.unipi.it

Abstract

In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional program including upregulation of the CXCL10 chemokine, which stimulates proliferation and invasion. Furthermore, PPARgamma activators thiazolidinediones modulate CXCL10 secretion in normal thyroid cells (TFC), and inhibite PTC growth. Until now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs, nor the effect of PPARgamma activation. The effects of IFNgamma+TNFalpha stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPARgamma activation by thiazolidinediones, on CXCL10 secretion and proliferation in these cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was absent under basal conditions; a similar dose-dependent secretion of CXCL10 was induced by IFNgamma in both cell types. TNFalpha alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFNgamma+TNFalpha induced a synergistic CXCL10 release in both cell types; however, a more than ten times higher secretion was induced in PTCs. Treatment of TFC with the thiazolidinediones dose-dependently suppressed IFNgamma+TNFalpha-induced CXCL10 release, while stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by thiazolidinediones was observed only in PTCs. In conclusion, a dysregulation of the CXCL10 secretion has been shown in PTCs. In fact, a more than ten times higher CXCL10 secretion has been induced by IFNgamma+TNFalpha in PTCs with respect to TFC. Moreover, thiazolidinediones inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The effect of thiazolidinediones on CXCL10 was unrelated to the significant antiproliferative effect in PTCs.