It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in "primary cultures of human thyroid follicular cells" (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant. IFNgamma, IFNalpha and IFNbeta, dose dependently induced CXCL9 and CXCL10 release. TNFalpha alone had no effect. The combination of each of the IFNs with TNFalpha had a significant synergistic effect on CXCL9 and CXCL10 secretion. Treatment of TFC with rosiglitazone dose dependently inhibited the IFNs-stimulated CXCL9 and CXCL10 release. Compared with IFNalpha and IFNbeta, IFNgamma was the most potent stimulus of CXCL9 and CXCL10 secretion. In conclusion, IFNalpha, IFNbeta, IFNgamma and TNFalpha (synergistically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 by TFC, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPARgamma activation partially inhibits this process. (C) 2010 Elsevier Ltd. All rights reserved.

Interferon-alpha, -beta and -gamma induce CXCL9 and CXCL10 secretion by human thyrocytes: modulation by peroxisome proliferator-activated receptor-gamma agonists.

ANTONELLI, ALESSANDRO;Ferrari SM;Fallahi P;VITTI, PAOLO;FERRANNINI, ELEUTERIO
2010

Abstract

It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in "primary cultures of human thyroid follicular cells" (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant. IFNgamma, IFNalpha and IFNbeta, dose dependently induced CXCL9 and CXCL10 release. TNFalpha alone had no effect. The combination of each of the IFNs with TNFalpha had a significant synergistic effect on CXCL9 and CXCL10 secretion. Treatment of TFC with rosiglitazone dose dependently inhibited the IFNs-stimulated CXCL9 and CXCL10 release. Compared with IFNalpha and IFNbeta, IFNgamma was the most potent stimulus of CXCL9 and CXCL10 secretion. In conclusion, IFNalpha, IFNbeta, IFNgamma and TNFalpha (synergistically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 by TFC, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPARgamma activation partially inhibits this process. (C) 2010 Elsevier Ltd. All rights reserved.
Antonelli, Alessandro; Ferrari, Sm; Fallahi, P; Ghiri, E; Crescioli, C; Romagnani, P; Vitti, Paolo; Serio, M; Ferrannini, Eleuterio
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/205446
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 69
  • ???jsp.display-item.citation.isi??? 66
social impact