Dysregulated Interleukin -33/ST2 Pathway Perpetuates Chronic Inflammation in Hashimoto’s Thyroiditis

2019 ◽  
Vol 19 (7) ◽  
pp. 1012-1021 ◽  
Author(s):  
Xuan Wang ◽  
Xiaoqing Shao ◽  
Xinhao Liu ◽  
Qiu Qin ◽  
Jian Xu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Western Blot ◽  
Chronic Inflammation ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Tissue ◽  
Hashimoto's Thyroiditis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Interleukin 33

Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated. Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining. Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR. Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.

scholarly journals Heat stress combined with lipopolysaccharide alter the activity and superficial molecules of peripheral monocytes

2019 ◽  
Vol 33 ◽  
pp. 205873841982889
Author(s):  
Jiajing Luo ◽  
Yi Chen ◽  
Chengjia Ding ◽  
Jialing Qiu ◽  
Yulan Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Heat Stress ◽  
Western Blot ◽  
Inflammatory Mediators ◽  
Peripheral Blood ◽  
Heat Stroke ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Rt Pcr ◽  
Tnf Α

The purpose of this study was to focus on the underlying relationship between the hyperactivity for the peripheral monocytes and heat stroke by investigating the inflammatory oxidative activity of and the expression of superficial molecules. Peripheral blood samples were collected from 10 healthy adult volunteers. Human blood monocytes were isolated by density gradient centrifugation and sequent adherent culture. The objectives were divided into four groups: 43°C heat stress combined with lipopolysaccharide (LPS) group, 43°C heat stress group, LPS group, and control group. There were 10 cases in each group. An enzyme-linked immunosorbent assay (ELISA) test was used to measure the concentrations of supernatant inflammatory mediators (tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10)). After loaded by 2,7-Dichlorodi-hydrofluorescein-diacetate (DCFHDA) fluorescent probe, intracellular reactive oxygen species (ROS) levels were determined by a flow cytometry. After fluorescent microspheres incubation, the phagocytosis of monocytes was observed under a fluorescent microscope. Respectively, the flow cytometry and Western blot were used to evaluate the level of triggering receptor expressed on myeloid cells-1 (TREM-1) and Toll-like receptor-4 (TLR-4) on the monocytes. Furthermore, the mRNA expression of TREM-1 and TLR-4 was detected by real-time polymerase chain reaction (RT-PCR). The heat stress combined with LPS stimulation promoted the peripheral monocytes to produce inflammatory mediators (TNF-α, IL-1β, and IL-10) and release ROS. Otherwise, such complex strike significantly suppressed the phagocytic activity of monocytes in peripheral blood. Moreover, the expression of TREM-1, TLR-4 and CD86 was measured by the flow cytometry on peripheral monocytes which were respectively promoted by the union of heat stress and LPS. The results of Western blot and RT-PCR demonstrated the similar kinetics on these superficial molecules (TREM-1, TLR-4, and CD86) stimulated by the combination of heat stress and LPS. The underlying mechanism of the dysfunction for the peripheral monocytes may be related to the abnormal expression of superficial molecules TREM-1, TLR-4, and CD86 on the monocytes induced by heat stress and LPS.

scholarly journals Evaluation of APRIL in serum of patients with Hashimoto’s Thyroiditis

2021 ◽  
Vol 16 (1) ◽  
pp. 46-51
Author(s):  
Adriana Carvalho Santos ◽  
Paulo Travassos Neto ◽  
Lia Rafaella Ballard Kuhnert ◽  
Marcelo Ribeiro Alves ◽  
Rita Vasconcellos ◽  
...  
Keyword(s):  
T Cells ◽  
Hashimoto’S Thyroiditis ◽  
Molecular Mechanisms ◽  
Cytotoxic T Cells ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Thyroid Peroxidase ◽  
Healthy Donors ◽  
Specific Receptors

Hashimoto’s thyroiditis (HT) is an autoimmune and inflammatory disease in which antibodies are directed against the thyroid gland leading to chronic inflammation and hypothyroidism. The autoimmunity against thyroid antigens can be associated to genetic background and environmental factors. Thyroid peroxidase (TPO) and thyroglobulin (TG) are the major autoantigens for characterizing the disease. HT is related to the activation of autoreactive CD4+ T cells, CD8+ cytotoxic T cells and antithyroid antibody producing-B cells. Among several cytokines related to the pathogenesis of HT, a proliferation-inducing ligand (APRIL) has been studied in the context of the establishment and/or maintenance of autoimmune diseases. The role of APRIL in the pathogenesis of HT is still poorly understood. Therefore, the present study aimed to compare APRIL serum concentration in HT patients and healthy donors by ELISA. We observed a significant decrease in APRIL concentration in HT patients when compared to the control group, and a positive correlation between APRIL level and age. Our results suggest that the APRIL molecule can compose the cytokine profile along the inflammatory response in HT, however, other investigations should be proposed to understand its molecular mechanisms via specific receptors and other regulatory loops.

scholarly journals LncRNA profile in Hashimoto’s thyroiditis and potential function of NONHSAT079547.2

2020 ◽  
Vol 64 (4) ◽  
pp. 259-270
Author(s):  
Jingyi Luo ◽  
Tingting Liu ◽  
Weiping Teng
Keyword(s):  
T Cells ◽  
Real Time ◽  
Potential Function ◽  
Real Time Pcr ◽  
Hashimoto’S Thyroiditis ◽  
Molecular Mechanisms ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Thyroid Peroxidase ◽  
Transcriptional Level

Hashimoto’s thyroiditis (HT) is a common organ-specific autoimmune disease, which develops in 0.3–1.5/1000 subjects annually. The aims of this study were to determine the lncRNA profile in peripheral blood CD4+ T cells from HT patients and then to characterize the potential function of NONHSAT079547.2. A total of 37 HT patients and 50 sex- and age-matched healthy controls were enrolled for high-throughput sequencing. Another 43 HT patients and 50 sex- and age-matched controls were enrolled for validation via real-time PCR. Flow cytometry and CCK8 assays were used to measure cell apoptosis and growth levels. Western blotting was used for measuring the expression of growth- and apoptosis-associated proteins. IL-17 serum concentration and transcriptional level in CD4+ T cells of participants were detected by ELISA and real-time PCR, respectively. The mechanism of competitive endogenous RNA was determined using real-time PCR, ELISA, RNA immunoprecipitation, and dual-luciferase assays in Jurkat cells. A total of 7564 significantly differentially expressed lncRNAs were found, of which 3913 lncRNAs were upregulated and 3651 lncRNAs were downregulated in HT group when compared to control group. NONHSAT079547.2 was significantly upregulated in HT patients and was positively correlated with serum thyroid peroxidase antibody level. Further studies confirmed that NONHSAT079547.2 could promote cell growth and control IL-17 expression and secretion via the NONHSAT079547.2/miR-4716-5p/IL-17 axis.This is the first study to describe the lncRNA profile in CD4+ T cells of HT patients. The studies on the function of NONHSAT079547.2 might elucidate the underlying molecular mechanisms and represent potential biomarkers for HT.

Vitamin D Treatment in Patients with Hashimoto’s Thyroiditis may Decrease the Development of Hypothyroidism

2016 ◽  
Vol 86 (1-2) ◽  
pp. 9-17 ◽  
Author(s):  
Bekir Ucan ◽  
Mustafa Sahin ◽  
Muyesser Sayki Arslan ◽  
Nujen Colak Bozkurt ◽  
Muhammed Kizilgul ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Hashimoto’S Thyroiditis ◽  
Healthy Control Group ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Endocrine Society ◽  
Thyroid Autoantibody ◽  
Healthy Control ◽  
The Mean

Abstract.The relationship between Hashimoto’s thyroiditis and vitamin D has been demonstrated in several studies. The aim of the present study was to evaluate vitamin D concentrations in patients with Hashimoto’s thyroiditis, the effect of vitamin D therapy on the course of disease, and to determine changes in thyroid autoantibody status and cardiovascular risk after vitamin D therapy. We included 75 patients with Hashimoto’s thyroiditis and 43 healthy individuals. Vitamin D deficiency is defined as a 25-hydroxy vitamin D (25(OH)D3) concentration less than 20ng/mL. Vitamin D deficient patients were given 50.000 units of 25(OH)D3 weekly for eight weeks in accordance with the Endocrine Society guidelines. All evaluations were repeated after 2 months of treatment. Patients with Hashimoto’s thyroiditis had significantly lower vitamin D concentrations compared with the controls (9.37±0.69 ng/mL vs 11.95±1.01 ng/mL, p < 0.05, respectively). Thyroid autoantibodies were significantly decreased by vitamin D replacement treatment in patients with euthyroid Hashimoto’s thyroiditis. Also, HDL cholesterol concentrations improved in the euthyroid Hashimoto group after treatment. The mean free thyroxine (fT4) concentrations were 0.89±0.02 ng/dL in patients with Hashimoto’s thyroiditis and 1.07±0.03 ng/dL in the healthy control group (p < 0.001). The mean thyroid volumes were 7.71±0.44 mL in patients with Hashimoto’s thyroiditis and 5.46±0.63 mL in the healthy control group (p < 0.01). Vitamin D deficiency is frequent in Hashimoto’s thyroiditis and treatment of patients with this condition with Vitamin D may slow down the course of development of hypothyroidism and also decrease cardiovascular risks in these patients. Vitamin D measurement and replacement may be critical in these patients.

Hashimoto's thyroiditis in a patient with ectopic thyroid tissue

2017 ◽  
Author(s):  
Nadia Khessairi ◽  
Ibtissem Oueslati ◽  
Ons Rjeb ◽  
Fatma Chaker ◽  
Meriem Yazidi ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Thyroid Tissue ◽  
Ectopic Thyroid ◽  
Hashimoto's Thyroiditis ◽  
Ectopic Thyroid Tissue

Salivary gland function in women with Hashimoto’s thyroiditis without xerostomia and the correlation with auto-thyroid antibodies

2020 ◽  
Author(s):  
Xiao-an Pang ◽  
Zhi-xiao Wei ◽  
Jun-hong Li ◽  
Xiao-qi Pang
Keyword(s):  
Salivary Gland ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Stimulating Hormone ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Thyroid Peroxidase ◽  
Thyroid Autoantibody ◽  
Submandibular Glands ◽  
Quantitative Parameters ◽  
Salivary Function

Abstract Background Hashimoto’s thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function. Methods Sixty consecutive subjects were included, comprising 32 women (mean age, 36 ± 12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40 ± 12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti– HT, Anti+ HT, Anti– DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. Results None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (p < 0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤ 0.05). Conclusion Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.

scholarly journals Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

2021 ◽  
Author(s):  
Runhong Yu ◽  
Shiwei Yang ◽  
Yufeng Liu ◽  
Zunmin Zhu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Western Blot ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Immunohistochemical Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Children ◽  
Expression Levels ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Purpose: Study was by intention to screen serum autoantibodies that may contribute to the early detection of B-cell acute lymphoblastic leukemia (B-ALL) in children.Patients and methods: The total protein from three pooled B-ALL cell lines(NALM-6, REH and BALL-1 cells) was separated using two-dimensional gel electrophoresis(2-DE), which was followed by Western blot by mixed serum from B-ALL patients (n=20) or healthy children(n=20). We obtained and analyzed the images of 2-D gel and Western blot by PDQuest software,and then identify the spots of immune responses in B-ALL samples compared with those in control samples.The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against α-enolase and voltage-dependent anion-selective channel protein 1(VDAC1) were further validated on the use of enzyme-linked immunosorbent assay(ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis.Results: Six protein dots were identified with MS as Aconitase,apoptosis-inducing factor(AIF),dihydrolipoamide dehydrogenase(DLD), α-enolase,medium-chain acyl-CoA dehydrogenase(MCAD) and VDAC 1.The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23%, respectively, which were significantly higher than those in normal controls(4% and 0). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. Conclusion: This study incidates that α-enolase and VDAC1 may be the antigen associated with B-ALL .α-enolase and VDAC1 autoantibodies may develop into potential serological markers of B-ALL in children.Other proteins also need to be confirmed in a large number of serum samples.

scholarly journals Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto’s Thyroiditis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Xiao ◽  
Jianqing Liang ◽  
Sunqiang Liu ◽  
Qiongyue Zhang ◽  
Famin Xie ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Gene Expression Regulation ◽  
Cell Metabolism ◽  
Thyroid Tissue ◽  
Hashimoto's Thyroiditis ◽  
Spectrometric Analysis ◽  
Preclinical Model ◽  
Needle Puncture ◽  
Organoid Culture ◽  
Chemokine Ligand

Hashimoto’s thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone’s understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

scholarly journals Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis

2018 ◽  
Vol 45 (5) ◽  
pp. 1787-1796 ◽  
Author(s):  
Ling Li ◽  
Xiaolian Ding ◽  
Xuan Wang ◽  
Qiuming Yao ◽  
Xiaoqing Shao ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Zinc Finger Protein ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Control Group ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Significant Difference ◽  
Proliferation And Differentiation

Background/Aims: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. Methods: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. Results: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. Conclusion: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.

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