Iodide effect on mRNA expression levels of genes related to immunological function in cultured human thyroid follicles
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kanji Sato
PROVIDER: E-GEOD-16957 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Graves’ disease is characterized by goiter, palpitation and exophthalmos (Merseburg’s trias). However, a few patients develop exophthalmos even though their thyroid function is normal, a condition known as euthyroid Graves’ disease (EGD). It remains unknown why these patients remain euthyroid, even though they have potent thyroid-stimulating antibody (TSAb). To investigate whether the immunoglobulins (IgGs) obtained from EGD patients elicit thyroid hormone-releasing activity (THRA), thyroid follicles obtained from Graves’ patients were cultured in agarose-coated culture dishes, and 125I incorporated into the thyroid follicles and organic 125I (mainly de novo-synthesized 125I-T3+125I-T4) released into the culture medium by TSH or purified IgGs were determined as thyroid hormone-releasing activity (THRA). This thyroid follicle culture system allows maintenance of the Wolff-Chaikoff effect, and the expression of mRNA for the sodium-iodide symporter is decreased by high concentrations of iodide (10-6-10-4M) and therapeutic concentrations of amiodarone (1-2microM). hTSH elicited THRA most efficiently at 0.4-10 microU/ml, suggesting that thyroid function is controlled within the normal range of TSH concentration (0.4-4.0 microU/ml). All IgGs obtained from hyperthyroid Graves’ patients elicited THRA equivalent to more than 4.6 microU/ml hTSH. IgGs obtained from EGD patients also had potent THRA, whereas IgGs obtained from normal subjects and Graves’ patients in complete remission had no significant THRA. When thyroid follicles from Graves’ thyroid, into which a number of lymphocytes had infiltrated, were used, only slight THRA was elicited by bTSH or Graves’ IgGs, probably due to inflammatory cytokines produced by immunocompetent cells that could not be separated during gentle centrifugation. Indeed, when thyroid follicles were cultured with autologous intrathyroidal lymphocytes, interleukin-2 completely abolished TSH-induced THRA. When thyroid follicles were cultured with inflammatory cytokines (interleukin-1, tumor-necrosis factor-alpha, or interferon-gamma), each cytokine inhibited TSH-induced THRA in a concentration-dependent manner. These cytokines at lower concentrations synergistically and completely inhibited TSH-induced THRA. Microarray analyses of thyroid follicles cultured with IL-1alpha, TNF-alpha, or INF-gamma revealed decreased expression of mRNAs for TSHR, NIS, TPO and thyroglobulin, accompanied by increased expression of mRNAs for chemokines and cytokines. These findings suggest that IgGs obtained from patients with EGD have potent THRA in vitro, whereas in vivo, these IgGs are unable to elicit biological activity in the thyroid gland. Presumably, immunocompetent cells that infiltrate the thyroid gland produce inflammatory cytokines that synergistically inhibit thyroid function. Since a similar phenomenon may occur in the retroorbital tissues, these patients may develop exophthalmos despite having a normal serum level of TSH. This data will be published in Hyperthyroidism: Etiology, Diagnosis and Treatment (editor-in-chief;Dr.Frank Clumbus,Nova Science Publishers, Inc, New York, USA) Experiment Overall Design: One conditioned experiments: control vs. IL-1 alpha 5ng/ml, cultured for 24 hours; control vs. TNF alpha 20ng/ml, cultured for 24 hours; control vs. IFN gamma 1000U/ml, cultured for 48 hours.
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Project description:Although viral infection is thought to be associated with subacute thyroiditis and probably with autoimmune thyroid disease, possible changes in thyroid function during the prodromal period of infection or subclinical infection remain largely unknown. Recently, it was shown that pathogen-associated molecular patterns stimulate Toll-like receptors (TLR) and activate innate immune responses by producing type I interferons (IFN). Using a human thyroid follicle culture system, in which de novo synthesized thyroid hormones are released into the culture medium under physiological concentrations of hTSH, we studied the effects of polyinosinic-polycytidylic acid (Poly(I:C)), a chemical analog of viral double-stranded RNA (dsRNA), on TSH-induced thyroid function. Thyrocytes expressed ligands for dsRNA (TLR 3, CD14, and RIG-1) comparable to the TSH receptor. DNA microarray and real-time PCR analyses revealed that dsRNA increased the expression of mRNA for TLR3, IFN-g, interferon-regulating factors, proinflammatory cytokines, and class I MHC, whereas genes associated with thyroid hormonogenesis (NIS, peroxidase, deiodinases) were suppressed. In accordance to these data, Poly(I:C) suppressed TSH-induced 125I uptake and hormone synthesis dose-dependently, accompanied by a decrease in the ratio of 125I-T3/125I-T4 released into the culture medium, whereas peptidoglycan, lipopolysaccharides, or unmethylated CpG DNA, ligands for TLR2, TLR4, and TLR9, respectively, had no significant effect. These inhibitory effects of Poly(I:C) were not blocked by a neutralizing antibody against TLR3 and an anti-IFN alpha/beta receptor antibody. These in vitro findings suggest that when thyrocytes are infected with certain viruses, dsRNA formed intracellularly in thyrocytes may be a cause for thyroid dysfunction, leading to development of autoimmune thyroiditis. This data was published in Endocrinology, vol.148, 3226-3235, 2007. Experiment Overall Design: Two conditioned experimets, control vs. double-stranded RNA (polyI-C), cultured for 6
2008-10-21 | E-GEOD-12154 | biostudies-arrayexpress
Project description:We are going to submit a paper entitled “Iodide-induced Chemokines and Genes Related to Immunological Function in Cultured Human Thyroid Follicles” to THYROID
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2024-08-29 | E-MTAB-13502 | biostudies-arrayexpress
Project description:Mouse RNA-Seq: cells derived from recombinant embryonic stem cell line (A2LoxNkx2-1-Pax8) were used. Mouse embryonic stem cell-derived thyroid follicles were exposed to a dose range of phthalates (DEHP, DIDP, DINP at 1-10-100 nM-1-10 uM; DnOP at 2-20-200 nM-2-20 uM) for 24 hours. Every condition was performed in triplicate. Untreated (n = 2) and 0.5% DMSO solvent (n = 5) controls were included. Combined mRNA/miRNA libraries were prepared and RNA-Seq performed. Human ATAC-seq: the human epithelial thyroid cell line, Nthy-ori 3-1, was exposed to DEHP or DINP for 5 days (n = 6), and ATAC-Seq was performed. 0.5% DMSO control samples (n = 6) were included.
2023-09-03 | E-MTAB-12830 | biostudies-arrayexpress
Project description:Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.
2022-05-20 | PXD026395 | Pride
Project description:The human epithelial follicular cell line Nthy-ori 3-1 was treated with 10 uM or 1 uM benzo[a]pyrene in 0.5% DMSO or with 0.5% DMSO only for 24 hours. Thyroid follicles were differentiated from a recombinant mESC line (A2LoxNkx2-1-Pax8) and treated with 0.5% DMSO for 24 hours. For Nthy-ori 3-1 samples, total RNA was extracted and used to prepare combined mRNA/miRNA libraries, poly(A) libraries and small RNA libraries. For thyroid follicles samples, total RNA was extracted and used to prepare combined mRNA/miRNA libraries.
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Project description:While thyroid nodules per se are frequent (4%–50%), thyroid cancer is rare (∼5% of all thyroid nodules). The minimally invasive Fine Needle Aspiration Cytology (FNAC) is the current gold standard for the diagnosis thyroid nodule malignancy. However, proper discrimination of follicular neoplasias often require more invasive diagnostic techniques. To develop a novel molecular classification system for thyroid cancer malignancy, we performed a genome-wide epigenetic profiling of 54 fresh frozen Follicular like thyroid samples using the Illumina Human DNA Methylation EPIC platform.
2022-09-01 | E-MTAB-10906 | biostudies-arrayexpress
Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples. RNA was extracted from flash frozen patient tumor and normal samples. Gene array analysis was performed, and resulting expression levels were compared between normal and tumor samples.
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Project description:Background. Radioiodide 131I is commonly used to treat thyroid cancer and hyperthyroidism, and 131I releases during nuclear accidents have resulted in increased incidence of thyroid cancer in children. To develop a better understanding of underlying cellular mechanisms behind 131I exposure and identify potential biomarkers, the aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats. Materials and methods. Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1–1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression patterns in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). Results. Nine 131I exposure-related biomarkers (Afp and RT1-Bb,ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Four dose-related biomarker candidates (APRT, LDHA) and (TGM3 and DSG4) were identified in thyroid and plasma, respectively. Candidate biomarkers for thyroid function were the upstream regulator PPARG and the proteins ACADL and SORBS2 (all activities), TPO and TG (low activities)). 131I exposure was shown to have a profound effect on metabolism, the immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated. Conclusion. Exposure-related and dose-related effects on gene and protein expression were observed, thereby identifying several candidate genes that could be used as potential biomarkers for exposure, absorbed dose and thyroid function.
2020-12-07 | PXD017715 | Pride