| Apoptosis is a process of self destruction that requires the activation of a genetic programme that may lead to changes in cell morphology, DNA fragmentation, and protein cross linking. More or less apoptosis than normal may lead to some diseases. Apoptosis involves the sequential activation of a series of caspases, which can degrade a number of death substrates. Caspase is activated by the mitochondrial pathway and the death receptor pathway. The most common pathway is death receptor pathway. Most of death receptors in this pathway belong to the tumour necrosis factor receptor superfamily. Interaction of these receptors with their ligands can induce cell death by the activation of various kinase enzymes that act as secondary messengers in the cell.The pathogenesis of autoimmune thyroid disease remains- 5 -unclear. Hashimoto's thyroiditis is characterized by existing of thyroid antibody, diffuse lymphocyte infiltration of the thyroid, thyroid follicle atrophy and destruction. The percentage of in situ apoptotic thyrocytes increases in Hashimoto's thyroiditis, suggesting that apoptosis has an important role in pathogenesis of this disease. Recent evidence shows that autocrine or paracrine interaction between Fas and FasL is a major mechanism in the autoimmune destruction of thyrocytes. The expression of the Fas and apoptosis of thyrocytes have been reported to increase after treatment with inflammatory cytokine interferon- y , interleukin-10, interleukin-1 3 and tumour necrosis factor- a . The roles of bcl-2 and bax proto-oncogene are important inthe regulation of the death pathways in the thyroid. Expression of Bcl-2 and Bax and the ratio between Bcl-2 and Bax could regulate the apoptosis.Regulation of apoptosis is an effective way to treat tumours. This could be achieved by inhibiting the apoptotic response in normal tissues or increasing the apoptotic response to cancerous tissues. A recent study showed Fas, TRAILR1, and TRAILR2 expressed in thyroid carcinoma cell lines respectively. According to immunohistochemical and mRNA studies, expressions of Fas and FasL are upregulated in adenoma, well-differentiated papillary and follicular carcinomas. In contrast, Fas and FasL is reduced in undifferentiated carcinoma. Recombinant TRAIL- 6 -activated caspase-10 at the receptor level and triggered an apoptotic cascade in some thyroid carcinoma cell lines. In contrast, the medullary carcinoma cell line was resistant to Fas and TRAIL induced apoptosis, even in the presence of cyclohemixide (CHX). This showed that TRAIL effectively kills thyroid carcinoma cells through apoptosis. These findings provide a potentially therapy against thyroid cancer.TRAIL and TRAILR are members of TNF superfamily and TNFR superfamily. Interaction between TRAIL and its death receptors can induce apoptosis of many sorts of tumour cells in vitro. Expression of TRAIL messenger RNA is constitutive in many tissues. Apoptosis that TRAIL induced can not be blocked by soluble Fas and TNFR, which suggests that apoptosis induced by TRAIL isn't similar to death pathway that Fas and TNFR induced. TRAILR include death receptor 4, death receptor 5, decoy receptor 1 and decoy receptor 2. TRAIL triggers rapid apoptosis in many tumour cell lines through binding its death receptor 4 and/or death receptor 5. Decoy receptor 1 lacks a cytoplasmic tail and decoy receptor 2 has a truncated cytoplasmic death domain, both ofthem compete with death receptor 4 and death receptor 5 for binding to TRAIL, so their transfection inhibits apoptosis TRAIL which induced.Apoptosis of the thyroid follicular cells has an important role in the pathogenesis of Hashimoto's thyroiditis and thyroid cancer. More information is needed before apoptosis can be- 7 -applied to treat these diseases. We examined the expression and cellular localization in thyroid of Hashimoto's thyroiditis, thyroid carcinoma, nontoxic thyroid goitor and normal thyroid by immunohistochemical ABC method and the quantitative analysis of the immunostaining by image analysis... |
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