Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells. 138 Oct 35

Cytokine mRNA production in the thyroid tissues of patients with various thyroid diseases was analysed by in situ hybridization. In addition, infiltrating leukocytes were characterized by immunohistologic studies using the alkaline phosphatase anti-alkaline phosphatase (APAAP) staining technique. The following clinical material was investigated: two cases of Graves' disease, one with high and the other with a low amount of infiltrating leukocytes as well as two cases of non-toxic goitre also showing considerable quantities of infiltrating cells. The hybridization was performed on tissue sections with antisense probes for interferon-gamma (IFN-gamma), IFN-alpha E, IFN-beta, interleukin-6 (IL-6) and IL-1 beta. A small number of individual cells were found to express high levels of mRNA for IFN-gamma, IL-1 beta and measurable amounts of IL-6 throughout the tissue sections. However, IFN-alpha E or IFN-beta were not detected. Cytokine expressing cells were noted in the tissue of one patient with Graves' disease and in two cases with non-toxic goitre. In these samples a high amount of infiltrating leukocytes (CD45+) was detected, especially CD3+, CD8+, CD4+ and CD45RA+ T cells, in addition to B cells and macrophages. In one case an unusually large amount of T cell receptor gamma/delta+ (TcR gamma/delta+) cells was found. However, one sample of thyroid tissue derived from a patient with Graves' disease was poorly infiltrated and showed few cells expressing cytokines. In conclusion, using thyroid tissue as an example, our data suggest that the application of in situ hybridization with antisense RNA permits the study of cytokine production in tissues of both autoimmune and non-autoimmune origin.
 ...
PMID:In situ hybridization of the mRNA for interferon-gamma, interferon-alpha E, interferon-beta, interleukin-1 beta and interleukin-6 and characterization of infiltrating cells in thyroid tissues. 153 76

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.
 ...
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.
 ...
PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor-alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony-stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease.
 ...
PMID:Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy. 190 94

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.
 ...
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.
 ...
PMID:Regulation of interleukin-6 release by human thyrocytes. 217 56

The intrathyroidal production of Interferon gamma, tumour necrosis factor alpha and beta, Interleukin-1 alpha and beta, Interleukin-6, platelet-derived growth factor A and of transforming growth factor-beta was analysed in patients with autoimmune and non-autoimmune thyroid disease. Cytokines were assessed indirectly by slot blot mRNA analysis in fresh tissue samples (unpurified cells, infiltrating mononuclear cells and thyroid follicular cells), in thyroid follicular cells in primary culture, as well as in thyroid-derived T-cell clones. The production of Interleukin-1 alpha and beta, Interleukin-6 and transforming growth factor beta was additionally measured by bioassay. Cytokine production by thyroid-infiltrating mononuclear cells generally did not differ between autoimmune and non-autoimmune samples, the whole panel of all cytokines being found in freshly purified cells as well as in thyroid-derived T-cell clones from patient with Graves' disease, as well as with multinodular non-toxic goitre. Thyroid follicular cells produced Interleukin-1 alpha, Interleukin-6 and transforming growth factor beta. Interleukin-1 and Interleukin-6 production did not differ between thyroid follicular cells from autoimmune and non-autoimmune thyroids. Transforming growth factor beta was, however, lower in non-toxic goitre than in Graves' disease and in normal thyroid tissue, but could be increased by exposure of the cells to micromolar concentrations of iodide. This seemed of special interest, as transforming growth factor beta proved to inhibit thyroid follicular cell growth in response to known growth stimuli, such as insulin-like growth factor I or epidermal growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Intrathyroidal cytokine production in thyroid disease. 267 71

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.
 ...
PMID:Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. 268 Jan 82

There is now good evidence that anti-thyroid drugs such as methimazole have immunomodulatory effects which may be important in the treatment of patients with Graves' disease, but the immunological mechanisms by which these agents act are not clear. This study has examined the effect of methimazole on four important soluble mediators of the immune response, interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-interferon (gamma-IFN) and B-cell differentiation factor (BCDF). When peripheral blood mononuclear cells from normal subjects were stimulated with mitogens (phytohaemagglutinin, concanavalin A or pokeweed mitogen) in the presence of 10-100 mumol/l methimazole, there was an increase in IL-2 activity in the culture supernatants. This effect was apparent between 24 and 60 h: enhanced proliferation of T-cells was also seen in methimazole-supplemented cultures. There was no effect of the drug on IL-2 receptor expression or on IL-1 and gamma-IFN production. BCDF was increased by methimazole in one of three experiments with pokeweed mitogen but not in three experiments with concanavalin A. These results suggest that the enhancement of mitogen-stimulated T-cell proliferation in vitro with methimazole is due to an increase in the IL-2 available to the T-cells in these cultures. Thus the in-vivo immunological effects of these drugs are likely to be complex since they may have at least two, possibly related, actions on the intrathyroidal lymphoid infiltrate, namely inhibiting oxygen radical generation and increasing IL-2 levels.
 ...
PMID:Effect of the anti-thyroid drug methimazole on interleukin-1 and interleukin-2 levels in vitro. 309 61


1 2 3 4 Next >>