Serum Soloble Fas in Autoimmune Thyroid Disease / 대한내분비학회지

The Changes of soluble Fas levels in Patients with Autoimmune Thyroid Diseases BACKGROUD: Apoptosis was observed in thyroid tissue from Hashimoto disease but not those from Graves disease. Recently Fas and Fas ligand interactions among thyrocytes were suggested to development of clinical hypothyroidism in Hashimoto disease.Soluble Fas produced as the form lacking the tranmembrane domain due to alternative splicing, is supposed to inhibit Fas-Fas ligand interaction and blocks Fas mediated apoptosis. METHODS: In tbis study, we measured serum soluble Fas to determine the possible involvement of this molecule in the autoimmune thyroid disease by enzyme linked immunosorbant assay in 29 patients with Graves disease, 30 patients with Hashimotos disease and 19 normal controls. RESULTS: Compared with normal subjeets (4.26 +/- 1.00 U/mL), soluble Fas was not increased in patients with Graves disease (4.23 +/- 1.14 U/mL, p>0.05) but it was increased in throtoxic Graves patients (4.70 +/- 1.26 U/mL, p<0.05) compared to euthyroid Graves (3.72 +/- 0.73 U/mL, p<0.05) and normal subjects (4.26 +/- 1.00 U/mL, p<0.05). The euthyroid and hypothyroid patients with Hashimoto disease showed low soluble Fas levels, 2.94 +/- 0.54 U/mL and 2.74 U/mL, respectively compare to the patients with Graves disease and normal subjects. The thyroid hormone levels to (T3 T4 and free T4) showed positive correlation with the serum titers of antithyroid autoantibodies, antithyroglobuin antibodies, antiperoxidase antibodies and thyrotropin binding inhibitor immunoglobulins. CONCLUSION: We found that the patients with thyrotoxic Graves disease had increased level of serum soluble Fas and the patients with Hashimoto disease showed low levels of soluble Fas compared to normal controls. Increased soluble Fas in Graves disease suggests increased expression of alternatively spliced Fas mRNA variant and decreased soluble Fas in Hashimoto disease suggests decreased Fas mRNA variant and increased full length membrane Fas, so these findings are related to the promotion of apoptosis of thyroid cells during autoimmune reaction in Hashimotos disease.

Hormonal regulation of ICAM-1 gene expression in thyroid cells, FRTL-5

Our previous works have shown that human thyroid follicular cells from Graves' disease and FRTL-5 rat thyroid cells express the intercellular adhesion molecule-1 (ICAM-1) molecule and its expression is upregulated by several cytokines, interferon-gamma, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6. We used FRTL-5 cells which show hormonal dependence of growth and function for the study of hormonal regulation of ICAM-1 gene, We studied ICAM-1 mRNA expression and promoter regulation after cloning of rat ICAM-1 promoter. We found very interesting findings that thyroid stimulating hormone (TSH) and forskolin downregulates steady state MHC class land ICAM-1 mRNA levels in FRTL-5 cells; furthermore, TSH/cAMP inhibit cytokines (interferon-gamma,tumor necrosis factor-alpha)-mediated maximal ICAM-1 mRNA expression, In addition, hydrocortisone and insulin differentially regulate the ICAM-1 mRNA levels; hydrocortisone markedly suppresses the mRNA level but insulin partially recovers hydrocortisone mediated ICAM-1 suppression, The interferon-gamma and tumor necrosis factor-alpha increases full ICAM-1 promoter (pCAM-1822) activity and this cytokine mediated increase of the promoter activity is also inhibited by TSH and forskolin, Thus TSH/cAMP pathways play roles as a antagonistic action for maximal expression of ICAM-1 gene by these cytokines. We propose this TSH action is one of physiologic mechanisms to preserve self tolerance in face of abnormal cytokine challenges in systemic inflammatory condition or acute phase response.

The Changes of Serum Soluble Intercellular Adhesion Molecule-1(ICAM-1) According to the Clinical Course of Graves' Disease Treated with Antithyroid Drug / 대한내분비학회지

Background: TSH binding inhibiting imunoglobulins(TBII) are autoimmune antibody causing autoimmune thyroid diseases such as Graves disease or Hashimoto's thyroiditis, while intercellular adhesion molecule-1(ICAM-1) is known as a substance expressed at the site of autoimmune reaction in relation with lymphocyte infiltration. The serum TBII activity is used as an index of the disease course and prognosis of Graves disease treated with antithyroid drugs, propylthiouracil or methimazole. The aim of this study is to understand the change of serum ICAM-1 level according to the change of the degree of autoimmunity and clinical course of Graves disease. Methods: In order to study the change of soluble ICAM-1 and relationship to the immune mechanism of Graves' disease, we measured serum levels of TBII and ICAM-1 in patients(n 35) with Graves disease before and after treatment with antithyroid drugs and in relapsed patients using a highly sensitive ELISA method. Results: The serum levels of TBII and ICAM-1 were markedly elevated in patients with Graves disease before treatment than normal controls and there were good correlation between TBII and ICAM-1 level. In patients with normalized TBII levels after 22 months antithyroid drug treatment, the ICAM-1 levels became normal but in the patients with high serum TBII level showed high serum level of ICAM-1 even with clinical remission with same treatment. The serum levels of TBII and ICAM-1 in relapsed patients were elevated as those of patients before treatment. Conclusion: With the above results, we can conclude that not only the TBII level but seru ICAM-1 level also reflect the degree of autoimmune activity of Graves disease and may be used as an index of the disease course and prognosis of Graves disease treated with antithyroid drugs.