Bossowski A, Czarnocka B, Bardadin K, Stasiak-Barmuta A, Urban M, Dadan J, Ratomski K, Bossowska A
2nd Department of Children's Diseases, Medical University of Bialystok, Bialystok, Poland.
Autoimmunity. 2008 Mar;41(2):163-73. doi: 10.1080/08916930701727749.
Apoptosis, i.e. natural programmed cell death, is a physiological phenomenon indispensable for normal functioning of the organism. The signal to apoptosis can be started practically in any cell. Disturbances in the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of the study was to assess the expression of Fas/FasL and caspase eight in the tissues of the thyroid gland in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). The analysis of Fas/FasL expression was performed by western blot and immunohistochemical investigation with DAB-visualization and Mayer's hematoxylin staining. Caspase-8 expression in thyroid follicular cells was assayed by western blot method. Identification of the proapoptotic proteins FasL and Fas exhibited their pronounced expression in the thyroid tissue in GD patients (++; ++) and HT (+++; +++) as compared to the NTNG group (0/+; 0/+). Among the study groups, the expression of caspase-8 was revealed in band 55 kDa from patients with autoimmune thyroid diseases. In GD patients, the percentage of thyrocytes with FasL expression correlated positively with TRAb (R = 0.58, p < 0.02). However, no such correlations were noted in HT or non-toxic multinodular goiter. There were no significant correlations between thyroid hormones and the percentage of thyrocytes with Fas and FasL expression. In conclusion, our findings suggest that the changes in the expression of apoptotic molecules on the surface of T lymphocytes and thyroid follicular cells in patients with autoimmune thyroid disorders reflect their substantial involvement in the pathogenesis of GD and HT. In addition, analysis of Fas/FasL and caspase-8 expression in thyroid tissue may indicate the disease activity and immunological phenotype.
细胞凋亡,即自然程序性细胞死亡,是机体正常功能所必需的一种生理现象。细胞凋亡信号几乎可在任何细胞中启动。细胞凋亡调控紊乱是包括自身免疫性甲状腺疾病在内的许多疾病发病机制的关键环节。本研究旨在评估Graves病(GD)、非毒性结节性甲状腺肿(NTNG)和桥本甲状腺炎(HT)患者甲状腺组织中Fas/FasL和半胱天冬酶8的表达。采用蛋白质免疫印迹法以及DAB显色和苏木精染色的免疫组织化学方法分析Fas/FasL的表达。采用蛋白质免疫印迹法检测甲状腺滤泡细胞中半胱天冬酶8的表达。与NTNG组(0/+;0/+)相比,GD患者(++;++)和HT患者(+++;+++)甲状腺组织中促凋亡蛋白FasL和Fas表达明显。在各研究组中,自身免疫性甲状腺疾病患者在55 kDa条带中检测到半胱天冬酶8的表达。在GD患者中,FasL表达阳性的甲状腺细胞百分比与促甲状腺素受体抗体(TRAb)呈正相关(R = 0.58,p < 0.02)。然而,在HT或非毒性多结节性甲状腺肿患者中未发现此类相关性。甲状腺激素与Fas和FasL表达阳性的甲状腺细胞百分比之间无显著相关性。总之,我们的研究结果表明,自身免疫性甲状腺疾病患者T淋巴细胞和甲状腺滤泡细胞表面凋亡分子表达的变化反映了它们在GD和HT发病机制中的重要作用。此外,分析甲状腺组织中Fas/FasL和半胱天冬酶8的表达可能有助于判断疾病活动度和免疫表型。