interleukin-8 and Thyroiditis

Chemokines are chemotactic cytokines responsible for the attraction and recruitment of different cell types during leukocyte infiltration, the histopathological hallmark of autoimmunity. Previous data demonstrate that thyrocytes secrete CXC chemokines, particularly CXCL8 and CXCL10. However, the physiopathological significance of such secretion and the effects of a combination of proinflammatory stimuli in terms of preferential CXCL8 and CXCL10 release remain unclear.. The aim of this study was to investigate whether the secretion of chemokines by human thyrocytes is a generalized inflammatory response or whether it is dependent upon specific proinflammatory stimuli.. CXCL8 and CXCL10 were measured in supernatants of human thyrocytes in primary cultures basally and after 24 h stimulation with interferon-γ (IFNγ) (1000 U/ml) and TNFα (10 ng/ml), alone or in combination.. CXCL8 but not CXCL10 was detected in basal conditions. The two chemokines showed differences in their response to proinflammatory cytokines. Indeed, significant secretion of CXCL10 was induced by IFNγ (P < 0.01) and not TNFα, whereas CXCL8 was secreted in response to TNFα (P < 0.01) being inhibited by IFNγ (P < 0.01). The combination of TNFα plus IFNγ synergistically increased the IFNγ-induced CXCL10 secretion (P < 0.01) and reversed the TNFα-induced CXCL8 secretion (P < 0.01).. These results confirm that human thyrocytes secrete CXC chemokines and demonstrate that the secretion of CXCL8 and CXCL10 is sustained by specific proinflammatory cytokines or their combination, which ultimately determines the nature of the infiltrating lymphocytes in human thyroid diseases. These results indirectly support a major role for CXCL10 in thyroid autoimmunity whereas CXCL8 might be involved in tumor-related inflammation.

Topics: Carcinoma; Cells, Cultured; Chemokine CXCL10; Chemokines, CXC; Diagnosis, Differential; Drug Evaluation, Preclinical; Humans; Inflammation Mediators; Interferon-gamma; Interleukin-8; Primary Cell Culture; Signal Transduction; Thyroid Gland; Thyroid Neoplasms; Thyroiditis; Thyroiditis, Autoimmune; Tumor Necrosis Factor-alpha

Autoimmune and non-autoimmune thyroiditis frequently occur in persons with hepatitis C virus (HCV) infection. Treatment with interferon alpha (IFNα) is also associated with significant risk for the development of thyroiditis. To explore HCV-thyroid interactions at a cellular level, we evaluated whether a human thyroid cell line (ML1) could be infected productively with HCV in vitro.. ML1 cells showed robust surface expression of the major HCV receptor CD81. Using a highly sensitive, strand-specific reverse transcription polymerase chain reaction assay, positive-sense and negative-sense HCV RNA were detected in ML1 cell lysates at days 3, 7, and 14 postinfection with HCV. HCV core protein was expressed at high levels in ML1 supernatants at days 1, 3, 5, 7, and 14 postinfection. The nonstructural protein NS5A was also detected in ML1 cell lysates by Western blotting. HCV entry into ML1 cells was shown to be dependent on the HCV entry factors CD81 and SR-B1/CLA1, while IFNα inhibited HCV replication in ML1 cells in a dose-dependent manner. Supernatants from HCV-infected ML1 cells were able to infect fresh ML1 cells productively, suggesting that infectious virions could be transferred from infected to naïve thyroid cells in vivo. Additionally, HCV infection of ML1 cells led to increased expression of the pro-inflammatory cytokine IL-8.. For the first time, we have demonstrated that HCV can infect human thyroid cells in vitro. These findings strongly suggest that HCV infection of thyrocytes may play a role in the association between chronic HCV infection and thyroid autoimmunity. Furthermore, the thyroid may serve as an extrahepatic reservoir for HCV viral replication, thus contributing to the persistence of viral infection and to the development of thyroid autoimmunity.

Topics: Autoimmunity; Cell Line; Hepacivirus; Hepatitis C; Humans; Interferon-alpha; Interleukin-8; Scavenger Receptors, Class B; Tetraspanin 28; Thyroid Gland; Thyroiditis; Viral Core Proteins; Viral Nonstructural Proteins; Virus Replication

The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity.. The clinical and molecular features, and the expression of inflammation-related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215).. The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0.001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAF(V600E) in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non-neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l-selectin was significantly higher in PTC specimens (either with RET/PTC, BRAF(V600E) or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l-selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues.. The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer.

Topics: Adolescent; Adult; Aged; Autoimmunity; Carcinoma, Papillary; Chemokine CCL20; Female; Genetic Association Studies; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Mutation; Oncogene Proteins, Fusion; Protein-Tyrosine Kinases; Proto-Oncogene Proteins B-raf; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Neoplasms; Thyroiditis; Young Adult