Interferon-gamma and Tumor Necrosis Factor-alpha Sustain Secretion of Specific CXC Chemokines in Human Thyrocytes: A First Step Toward a Differentiation between Autoimmune and Tumor-Related Inflammation?

摘要

different cell types during leukocyte infiltration, the histopathological hallmark of autoimmunity.\udPrevious data demonstrate that thyrocytes secrete CXC chemokines, particularly CXCL8 and\udCXCL10. However, the physiopathological significance of such secretion and the effects of a combination\udof proinflammatory stimuli in terms of preferential CXCL8 and CXCL10 release remain\udunclear.\udObjective: The aim of this study was to investigate whether the secretion of chemokines by human\udthyrocytes is a generalized inflammatory response or whether it is dependent upon specific proinflammatory\udstimuli.\udMethods: CXCL8 and CXCL10 were measured in supernatants of human thyrocytes in primary\udcultures basally and after 24 h stimulation with interferon- (IFN) (1000 U/ml) and TNF (10 ng/ml),\udalone or in combination.\udResults: CXCL8 but not CXCL10 was detected in basal conditions. The two chemokines showed\uddifferences in their response to proinflammatory cytokines. Indeed, significant secretion of\udCXCL10 was induced by IFN (P 0.01) and not TNF, whereas CXCL8 was secreted in response\udto TNF (P 0.01) being inhibited by IFN (P 0.01). The combination of TNF plus IFN\udsynergistically increased the IFN-induced CXCL10 secretion (P 0.01) and reversed the TNF-\udinduced CXCL8 secretion (P 0.01).\udConclusions: These results confirm that human thyrocytes secrete CXC chemokines and demonstrate\udthat the secretion of CXCL8 and CXCL10 is sustained by specific proinflammatory cytokines or their\udcombination, which ultimately determines the nature of the infiltrating lymphocytes inhumanthyroid\uddiseases. These results indirectly support a major role for CXCL10 in thyroid autoimmunity whereas\udCXCL8 might be involved in tumor-related inflammation.