Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid cells are exposed to complement attack in Graves' disease and Hashimoto's thyroiditis, but are resistant to killing by homologous complement. We have examined the effects of sublethal complement attack on thyroid cells in vitro. Extracellular reactive oxygen metabolites were produced and prostaglandin E2, interleukin-1 alpha, and interleukin-6 were released after complement attack. Cells pretreated with interferon-gamma and interleukin-1 alpha, which increase expression of CD59, were more resistant to these effects of complement. Conversely, blockade of CD59 with monoclonal antibody increased complement-mediated oxygen radical production and release of prostaglandin E2, interleukin-1 alpha, and interleukin-6. The antithyroid drugs methimazole and propylthiouracil abolished or reduced oxygen radical production by complement-attacked thyroid cells and reduced cytokine release. These results suggest that sublethal complement attack in autoimmune thyroid diseases exacerbates tissue injury by causing thyroid cells to release potent phlogistic mediators, although some degree of protection may be afforded in vivo by cytokine-mediated upregulation of CD59. Antithyroid drugs, concentrated within thyroid cells, will prevent the release of these inflammatory molecules, which may in turn explain the amelioration of thyroiditis and remission of Graves' disease after such treatment.
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PMID:Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells. 138 Oct 35

We have established previously that human thyroid epithelial cells (TEC) from patients with autoimmune thyroiditis are able to synthesize cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6). This paper examines TEC in sections from autoimmune thyroiditis for the in vivo production of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) using the combined techniques of in situ hybridization and immunohistochemistry. Thyroid tissue from patients with Graves' disease, Hashimoto's disease and non-toxic goitre was examined and both mRNA and the protein of TNF-alpha were detected in TEC on frozen sections. Representative figures of only Graves' samples are illustrated in this paper. In contrast, using the same methods, IFN-gamma was detected only in the infiltrating cells and not in TEC of thyroid tissue from the patients.
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PMID:Detection of in vivo production of tumour necrosis factor-alpha by human thyroid epithelial cells. 157 93

Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
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PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

Human endocrine thyroid epithelial cells have been described to produce cytokines in vitro. In order to determine whether they do so in vivo during thyroiditis, parallel studies on mRNA expression with a non-radioactive in situ hybridization technique and immunohistochemical detection for the protein were performed on frozen sections of thyroid samples from autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), non-toxic goitre and normal thyroid tissue. cDNA probes were sulphonated and their hybridization with mRNA was detected with a sulphonyl-specific monoclonal antibody. This signal was amplified and visualized with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) system. The protein products were detected with immuno-purified rabbit F(ab')2 antibody fragments recognizing recombinant human cytokines, visualized by the immunoperoxidase technique. Each sample was studied at the two levels. Both interleukin-6 mRNA and protein were found in the endocrine cells. There was no obvious difference between autoimmune thyroiditis and non-toxic goitre. However, normal thyroid epithelial cells produced less interleukin-6. Interleukin-1 alpha mRNA and its protein were found in epithelial cells from Hashimoto's thyroiditis samples, but not in the others, except one Graves' disease sample, in which only mRNA was detected. Interleukin-1 beta was not detected in these cells, its mRNA was only found in one of the Graves' disease samples. These cytokines were also detected in some infiltrating cells.
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PMID:Detection of interleukin-6 and interleukin-1 production in human thyroid epithelial cells by non-radioactive in situ hybridization and immunohistochemical methods. 199 63

Autoimmune thyroiditis is characterized by lymphocytic accumulation within the thyroid which may be the result, in part, of immunomodulatory cytokine secretion by thyrocytes. We have tested human thyroid cell cultures (n = 9) for interleukin-6 (IL-6) release using two bioassays. IL-6 was detected in all culture supernatants under basal conditions and was increased by gamma-interferon, tumour necrosis factor and TSH in a dose-dependent manner. The bioactivity was confirmed as IL-6 by immunoblotting experiments and could not be accounted for by contamination of the thyroid cell cultures with fibroblasts, lymphocytes or monocytes. Circulating IL-6 levels were not raised in patients with Graves' hyperthyroidism. Exogenous recombinant IL-6 reduced cyclic AMP production in response to TSH when added to thyroid cell cultures. Since IL-6 plays a major role in B cell differentiation and T cell activation, release of IL-6 by thyrocytes may increase the intrathyroidal autoimmune response in Graves' disease and Hashimoto's thyroditis. Our results also suggest that IL-6 may modulate thyroid cell function.
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PMID:Regulation of interleukin-6 release by human thyrocytes. 217 56

Cytokine production was studied in thyroid tissue from patients with Graves' disease, Hashimoto's thyroiditis and non-toxic goitre. The expression of interferon gamma, tumour necrosis factor alpha and beta, interleukin-1 alpha and beta, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1 alpha and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1 alpha and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vivo as both interleukin-1 and interleukin-6 facilitate T cell activation.
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PMID:Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. 268 Jan 82

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.
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PMID:Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders. 757 71

Interleukin-6 (IL-6) is a multifunctional cytokine involved in autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease. IL-6 is produced by infiltrating immune cells and by thyrocytes. In the latter cell type, secretion of IL-6 is stimulated notably by interleukin-1 (IL-1), thyroid-stimulating hormone (TSH) or forskolin (Fk), a cAMP elevating agent. We report here that Fk and IL-1 synergistically enhance IL-6 mRNA expression in FRTL-5 thyroid cells by mechanisms involving the cAMP/PKA pathway, and both stabilization of the IL-6 mRNA and activation of the IL-6 promoter. Point mutations or deletions of the main transcription factor binding sites in the IL-6 promoter indicated that the synergistic effect was mainly mediated by the AP-1 site, and that the CRE site contributed to this effect. The DNA binding activity of AP-1 transcription factors and the expression of c-Fos and Fra-2 proteins, were all enhanced when the cAMP and IL-1 signalling pathways were both stimulated. These findings contribute to elucidating the synergistic mechanisms that regulate IL-6 secretion by thyroid cells, and suggest that such mechanisms may be involved in the development of thyroid autoimmune disorders.
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PMID:Activation of the cAMP pathway synergistically increases IL-1-induced IL-6 gene expression in FRTL-5 thyroid cells: involvement of AP-1 transcription factors. 1828 Jun 40

We explored the role of interleukin-6 (IL-6) in the development of autoimmune thyroiditis in nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis, using anti-mouse IL-6 receptor antibody (MR16-1). Thyroiditis was induced by iodide ingestion or mouse thyroglobulin (Tg) immunization. Mice were injected intraperitoneally with saline, control rat IgG, or MR16-1 (2 or 8 mg). Iodide ingestion did not increase serum IL-6 levels and MR16-1 (2 mg) failed to prevent the development of thyroiditis. In contrast, Tg immunization induced a rapid and significant increase in serum IL-6 levels. While MR16-1 (2 mg) had no effect on Tg-induced thyroiditis, the severity, but not incidence, of thyroiditis was reduced in 8 mg MR16-1-treated mice compared with saline-injected mice. However, thyroiditis development in the 8 mg MR16-1-treated mice was indistinguishable from that in the control IgG-treated mice. MR16-1 (8 mg) did not affect serum anti-Tg antibody levels. These results suggest that IL-6 may play only a minor role in the development of autoimmune thyroiditis in NOD mice.
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PMID:Effects of interleukin-6 blockade on the development of autoimmune thyroiditis in nonobese diabetic mice. 1930 Dec 5

C-reactive protein (CRP) is an acute phase reactant synthesized by hepatocytes that is regulated by pro-inflammatory cytokines, particulary interleukin-6 (IL-6). Over the last decade, CRP has been reported to be associated with a poor prognosis in patients with various types of cancer. Although the mechanisms by which the systemic inflammatory response reflected by an elevated serum CRP level influences survival in patients with cancer have not been fully elucidated, several possibilities involving the activation of IL-6, thereby elevating the CRP level, in cancer patients have been proposed. With regard to hepatocellular carcinoma (HCC), since Hashimoto et al. first demonstrated that the preoperative serum CRP level is an independent and significant factor predictive of a poor prognosis in patients undergoing surgical resection, several investigators have identified an elevated serum CRP level to be an indicator of poor outcomes in HCC patients undergoing transplantation, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection and best supportive care. Recently, the CRP level has been reported to be clinically applicable as a marker of treatment outcomes in HCC patients. However, large-scale, prospective validation studies are needed to confirm these results.
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PMID:C-Reactive Protein as a Prognostic Marker in Patients with Hepatocellular Carcinoma. 2690 38


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