• CXCL11
• CXCL9
• papillary thyroid cancer
• PPARgamma.

Several studies agree in supporting of the basic role assumed by Interferon (IFN)-gamma-inducible chemokines [(C-X-C motif) ligand 9 (CXCL9) chemokine, CXCL10 and CXCL11] and their receptor, CXCR3 in the initial stage of autoimmune disorders involving endocrine glands. Indeed, under IFN-gamma stimulation, endocrine epithelial cells secrete CXCL10, which can recruit type 1 T helper lymphocytes, that in turn secrete IFN-gamma, thus initiating and perpetuating the autoimmune process. A connection between inflammation and cancer is well supported, in particular the pivotal role assumed by chemokines in the network of inflammatory mediators linked to neoplasia.
Until now, no study has evaluated CXCL9 and CXCL11 chemokines in thyroid cancer. Therefore, we investigated on the role of CXCL9, CXCL11 in papillary thyroid cancer (PTC) cells and their modulation by IFN-gamma, tumor necrosis factor (TNF)-alpha and peroxisome proliferator-activated receptor-gamma (PPAR)-gamma.
In this study we have demonstrated that: a) CXCL9, CXCL11 chemokines were basally absent in non-neoplastic thyroid (TFC) and PTC cells; b) IFN-gamma alone induced the chemokines secretion in TFC, and PTC; c) TNF-alpha alone induced chemokines secretion only in PTC; d) IFN-gamma+TNF-alpha induced a synergistic chemokines release in PTC, and at a lower level in TFC; e) PPAR-gamma agonists suppressed dose-dependently IFN-gamma+TNF-alpha-induced chemokines release in TFC; f) PPAR-gamma agonists stimulated dose-dependently IFN-gamma+TNF-alpha-induced chemokines release in PTC; g) PPAR-gamma knocking down, by RNA interference technique in PTC cells, abolished PPAR-gamma agonists effect on chemokines release; h) PPAR-gamma agonists reduced proliferation (P<0.01) in PTC cells; i) CXCL9 or CXCL11 (100 and 500 pg/mL) reduced proliferation and migration (P<0.01) in PTC cells.
In conclusion, we have seen that: in PTC cells there is a marked release of CXCL9 and CXCL11 which is induced by IFN-gamma+TNF-alpha; PPAR-gamma agonists stimulated CXCL9 and CXCL11 secretion, while inhibited proliferation; CXCL9 and CXCL11 inhibited proliferation and migration.