Cytokine production was studied in thyroid fine needle aspirates and peripheral blood and the production of interferon-gamma by peripheral blood mononuclear cell(PBMC) culture in response to interleukin-2(IL-2) stimulation was also studied from patients with hyperthyroidism, non toxic goiter, thyroid nodule. The expression of glycer aldehyde 3-phosphate dehydrogenase(GAPDH), interleukin-1beta(IL-1beta), IL-2, interleukin-8(IL-8), platelet- derived growth factor-A(PDGF-A) and interferon-gamma(IFN-gamma) chain was assessed by RT-PCR(reverse transcriptase polymerase chain reaction) in fine needle aspirates of thyroid and peripheral blood mononuclear cell : the samples were obtained from 7 patients with hyperthyroidism, 6 patients with non toxic goiter, 7 patients with thyroid nodule. A dose of IL-2(25 U/ml) was utilized to induce IFN-gamma production by PBMC from all patients.The results were as follows:1) In case of cytokine expression of fine-needle aspirates, GAPDH and IL-1beta, IL-8 were expressed highly but IFN-gamma, IL-2 were not expressed in hyperthyroidism and non-toxic goiter, thyroid nodule. PDGF-A was expressed in hyperthyroidism and thyroid nodule but not in non toxic goiter. 2) In case of cytokine expression of PBMC, GAPDH, IL-1beta were expressed in hyperthyroidism and non toxic goiter, thyroid nodule and highly expressed after IL-2 stimulation than before. But PDGF-A was more expressed in non toxic goiter and thyroid nodule than hyperthyroidism. Also, IFN-gamma was less expressed in thyroid nodule than hyperthyroidism and non toxic goiter. 3) The incremental increase in IFN-gamma value in supernatants of PBMC culture was significantly higher in patients with non toxic goiter than that in PBMC from hyperthyroidism and thyroid nodule(p<0.05).Therefore it seems that the cytokine production was found in hyperthyroidism and non toxic goiter and thyroid nodule. There were variability in their distribution each other, in general, higher expressed in hyperthyroidism than non toxic goiter. And RT-PCR Method that employed should be sufficiently sensitive to permit the analysis of cytokine gene expression in fine needle aspiration biopsies from patients with thyroid disease.
BACKGROUND Graves' disease (GD) is an organ-specific autoimmune disease that is characterized by lymphocyte infiltration of the thyroid, which finally leads to follicular destruction. The CD4+CD25+ regulatory T cells are important for maintaining peripheral tolerance to self-antigens and impaired activity can cause autoimmune diseases. CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily and expressed on activated T cells, is a candidate molecule for a co-stimulatory role in autoimmune thyroid disease. In this study, we aimed to assay the frequency of CD4+CD25+ T cells in GD patients and to investigate the role of CD137-mediated costimulation in CD4+CD25+ T cells. METHODS: The frequencies of the CD4+CD25+ T cells in the peripheral blood (PB) of GD patients were determined by flow cytometric analysis. After the CD4+CD25+ T cells were isolated from PB mononuclear cells (PBMC) of the GD patients using immunomagnetic beads, the functional activity of the CD4+CD25+ T cells was characterized by use of a proliferation assay. mRNA expression of Foxp 3 in the CD4+CD25+ T cells of the GD patients was observed by real-time RT-PCR. RESULTS: In this study, we found that GD patients had a low proportion of CD4+CD25+ T cells (mean +/- SD; 1.47 +/- 0.31%) in PBMC as compared with normal subjects. CD137-mediated costimulation increased the expression of CD25 and Foxp 3 in CD4+ T cells in GD patients as compared with normal subjects. Moreover, the CD137-mediated costimulation also induced the proliferation of CD4+CD25+ T cells in GD patients, and the expanded CD4+CD25+ T cells could suppress other CD4+CD25- T cells in a co-culture. CONCLUSION: These results suggest that the peripheral expansion of CD4+CD25+ T cells by CD137-mediated co-stimulation can suppress effector T cells and may be a potent therapy for Graves' disease.
Citations
Citations to this article as recorded by
Effects of Gastrodia elata Blume on Apoptotic Cell Death of Liver Cancer Cells by Expression of Bcl-2, Bax, and AMPKα Jae Hyun Park, Min Ho Kang, Ji Woo Hong, So Hee Kim, Yoon Seon Hwang, Jae Hoon Park, Jin Woo Kim Korean Journal of Medicinal Crop Science.2022; 30(5): 311. CrossRef
In Gul Moon, Ho Yeon Chung, Chang Sun Hwang, Young Soon Kang, Mi Sun Chung, Han Jin Oh, Kyu Hong Choi, Sun Woo Kim, Eui Hyun Kim, Youn Yee Kim, Chang Hoon Yim, Ki VOk Han, Hak Chul Jang, Hyun Koo Yoon, In Kwon Han
J Korean Endocr Soc. 2000;15(2):204-213. Published online January 1, 2001
BACKGROUND Osteoprotegerin(OPG) is a soluble member of the tumor necrosis factor(TNF) receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction between osteoblastic/stromal cells and osteoclast progenitors. OPG is expressed in many tissues including osteoblasts and may act on bone tissues in a paracrine and/or autocrine fashion. Futhermore, many cytokines and growth factors are known to influence the regulation of OPG expression in osteoblastic/stromal cells. The aims of the present study were to examine whether or not OPG was expressed in human peripheral blood mononuclear cells(PBMCs) and to investigate the effects of IL-1beta, which were known as potent osteotropic agents, on the regulation of OPG mRNA in PBMCs. METHODS: PBMCs were isolated by centrifugation over Ficoll-Hypaque density gradients from postmenopausal women and cultured in 6-well plates containing alpha-MEM supplemented with 5% FBS. The expression of OPG mRNA in PBMCs was observed by RT-PCR in adherent and nonadherent cells on culture plates. To observe the effect of OPG expression by IL-1beta, we measured the concentration of OPG mRNA by altering the concentration and incubation time of IL-1beta. The measurement of OPG mRNA was done by semi-quantitative PCR and indicated as OPG/GAPDH. RESULTS: OPG was expressed both in cells attached to the surface of culture plates and in non-adherent cells for the incubation of peripheral blood mononuclear cells. The effect of OPG mRNA by IL-1beta tend to increase in accordance with the length of incubation time and maximizes at 12 hours of incubation time and shows 1.2-3.5 times higher than the standard level at the concentration of 0.5ng/ml. However, the increased quantity in concentration varies according to individuals.] CONCLUSION: OPG mRNA is expressed in peripheral blood mononuclear cells and known to be increased by IL-1beta.