TRAIL Death Pathway Expression and Induction in Thyroid Follicular Cells

Bretz, James D.; Rymaszewski, Michal; Arscott, Patricia; Myc, Andrzej; Ain, Kenneth B.; Thompson, Norman W.; Baker, James R.

doi:10.1074/jbc.274.33.23627

Cited by 78 publications

(53 citation statements)

References 47 publications

(49 reference statements)

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“…Presence of CHX (1 mg/ml) signi®cantly enhanced TRAIL-induced apoptosis in both NPA ( Figure 1B(h)) and SW579 cell lines as more than 80% of cells were killed after 8 h incubation with TRAIL (200 ng/ml) and 97% apoptosis after 24 h ( Figure 2). Under the same conditions, normal thyroid follicular cells could not be killed by TRAIL (Bretz et al, 1999, and data not shown). Signi®cant apoptotic changes were not noted when thyroid cancer cells (NPA and SW 579 in particular) were treated with either TNF-a or agonistic Fas Ab (CH11) alone.…”

Section: Apoptosis Of Thyroid Cancer Cellsmentioning

confidence: 65%

“…Little is known however, whether the apoptotic machinery of thyroid cancer cells triggered by death-inducing cytokines is operational and can be activated for tumoricidal purposes. Bretz et al (1999) studied the e ect of in¯ammatory cytokines interferon g, TNF-a and interleukin-1b on the expression of TRAIL in thyroid cancer cell line KAT5, however, the mechanism of apoptosis triggered by TRAIL was not worked out. Recently, it has been reported that protein kinase C e is able to induce apoptotic cell death of thyroid cells (Knauf et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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TRAIL-induced apoptosis of thyroid cancer cells: potential for therapeutic intervention

Ahmad

Shi

2000

Oncogene

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To determine whether the apoptotic machinery of thyroid cancer cells is functional and could be activated for tumoricidal purposes, we examined the apoptosis induced by the cytokines TNF-a, Fas and TRAIL in thyroid cancer cell lines, NPA and SW579. Interestingly, out of these cytokines, only TRAIL was able to trigger signi®cant apoptosis. The tumoricidal e ect of TRAIL was further enhanced by CHX, suggesting the presence of CHX-sensitive inhibitor(s) of apoptosis in these thyroid cancer cell lines. The anti-apoptotic proteins like FLAME-1, Bcl-2 and Bcl-xL are believed to be such CHX-sensitive inhibitors in various types of cancer cells. We, however, provide the evidence using NPA and SW579 cell lines that these proteins were not a ected by the CHX treatment in thyroid cancer cells. The apoptosis of thyroid cancer cells was mediated by the classical activation of caspases that in turn activated the DNA Fragmentation Factor (DFF-45). To elucidate the role of individual caspases in TRAIL-mediated apoptosis, the inhibitory e ects of several general and speci®c tetrapeptide caspase inhibitors were studied. The inhibitors of caspase-1, -6, -8, and -9 as well as general upstream inhibitors of apoptosis could dramatically inhibit TRAIL-induced apoptosis in thyroid cancer cells. Caspase-2 and -3 inhibitors, on the other hand, had no signi®cant e ect. When the cells were treated with either agonistic Fas antibody (CH11) or TNF-a, no apoptotic changes were observed. The apoptosis induced by agonistic Fas Ab could be seen only after a prolonged exposure (24 h) to CHX, whereas TNF-a had no e ect even in the presence of CHX. The e cacy of TRAIL was also tested on other types of thyroid cancer cells like ARO, FRO (anaplastic carcinoma) and TPC-1 (papillary carcinoma) and compared to that triggered by other death inducing cytokines FasL and TNF-a. Again TRAIL was more potent in triggering apoptosis than Fas and TNF-a. Since TRAIL is e ective in selectively killing thyroid tumor cells without a ecting normal thyrocytes and also does not cause organ toxicity and in¯ammation in vivo, its potential for the treatment of thyroid cancer seems very promising.

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Section: Apoptosis Of Thyroid Cancer Cellsmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

TRAIL-induced apoptosis of thyroid cancer cells: potential for therapeutic intervention

Ahmad

Shi

2000

Oncogene

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“…Treatment with PI-PLC could remove the TRAIL-R3 receptors from the cell membrane [11,40]. As well, an inhibitor such as CHX suppressing protein synthesis might also influence the resistance of islet cells to the TRAIL death pathway [52]. Primary islet cells were found to be susceptible to apoptosis mediated by TRAIL, in the presence of the protein synthesis inhibitor CHX in this study.…”

Section: Discussionmentioning

confidence: 62%

“…However, not all transformed tumor cells are susceptible to the TRAIL death pathway [40,58]. The major factors that determine the susceptibility remain unclear [37,52]. There might be some unidentified changes not related to transformation leading to the susceptibility to TRAIL-mediated apoptosis in the primary beta cells.…”

Section: Discussionmentioning

confidence: 99%

TNF-Related Apoptosis-Inducing Ligand Death Pathway-Mediated Human Beta-Cell Destruction

Metzger

Wang

et al. 2002

Diabetologia

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Aims/hypothesis. The aim of this study is to investigate whether apoptosis in human beta cells can be related to the induction of the tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) pathway. Methods. We examined the expression of TRAIL and TRAIL receptors in two human pancreatic beta-cell lines and in human primary islet cells using RT-PCR assays and flow cytometric analyses and tested TRAIL-mediated beta-cell destruction in 51 Cr release cytotoxicity assays, Annexin-V and APO-DIREC assays.Results. Most of the human beta cells express TRAIL receptors-R1, -R2, -R3, -R4 and/or TRAIL. TRAIL induced much stronger cytotoxicity and apoptosis to beta-cell lines CM and HP62 than did FasL, TNF-α, LTα1β2, LTα2β1, LIGHT, and IFN-γ. The cytotoxicity and apoptosis induced by TRAIL to beta-cell lines CM were inhibited competitively by soluble TRAIL receptors, R1, R2, R3 or R4. Treatment of these beta cells with antibodies against TRAIL receptors was able to block the cytotoxicity of TRAIL to these cells. Beta-cell antigen-specific CTL (CD4 + and CD8 + ) clones express TRAIL, suggesting that these cells are potential sources of TRAIL-inducing betacell destruction. Normal primary islet cells from most donors are resistant to the cytotoxicity mediated by TRAIL. However, treatment with an inhibitor of protein synthesis (cycloheximide) or with an enzyme (PI-PLC) that can remove TRAIL-R3 from the isletcell membrane was able to increase the susceptibility of TRAIL-resistant primary islet cells to the TRAIL death pathway. Conclusion/interpretation. The TRAIL death pathway is present and can function in human islet beta cells, but unidentified inhibitors of the TRAIL death pathway are present in normal islet cells. [Diabetologia (2002[Diabetologia ( ) 45:1678[Diabetologia ( -1688

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“…Proinflammatory cytokines, such as TNF-α and IL1, can affect immunityrelated apoptosis. TNF-α and IL1 in combination with IFN-γ have been shown to induce apoptosis in thyroid cell culture studies [21][22][23] . The mechanism of apoptosis in HT seems to be associated with the stimulation of cytokines secreted from local lymphocytes 23 .…”

Section: Cumhuriyet Medical Journalmentioning

confidence: 99%

The effect of Vitamin D treatment on thyroid function and the levels of thyroid autoantibodies, TNF-α, IL-6, IL-1β in patients with autoimmune thyroiditis

Acibucu

Dökmetaş

Kilicli

et al. 2016

Cumhuriyet Medical Journal

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SUMMARYObjective: To investigate the relationship between autoimmune thyroid disease and vitamin D treatment. Method: Fifty four (54) patients with both vitamin D deficiency and newly diagnosed euthyroid Hashimoto's thyroiditis (HT) were recruited for this study. The patients were given intramuscular administration of cholecalciferol at a dose of 300,000 IU/month for 3 months. At the time of diagnoses and after the treatment of vitamin D, free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), antithyroid peroxidase (anti-TPO), antithyroglobulin (anti-TG), 25 (OH) D3, parathormone (PTH), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels were measured in all patients; TNF-a, IL-6 and IL-1ß levels were measured in only 43 patients. Results: A statistically significant difference (p˂0.05) was observed between the pre and post treatment FT4, TSH, antiTPO, antiTG, PTH and ALP levels. After the treatment of vitamin D, a statistically significant increase was found in 25 (OH) D3 and FT4 levels, and a significant decrease was found in TSH, antiTPO, antiTG, PTH and ALP levels, whereas no significant difference was noted in FT3, Ca, P, TNF-a, IL-6 and IL-1ß levels. Further, levels of vitamin D were not correlated with FT3, FT4, TSH, antiTPO, antiTG, TNF-a, IL-6 and IL-1ß levels (p˃0.05). CMJCumhuriyet Medical Journal stimulan hormon (TSH), anti tiroid peroksidaz (TPO) ve anti tiroglobulin (TG), 25(OH)D3, parathormon (PTH), kalsiyum (Ca), fosfor (P) ve alkalen fosfataz (ALP) seviyeleri ve yalnız 43 hastada TNF-α, IL-6, IL-1b seviyeleri ölçüldü. Bulgular: Tedavi öncesi ve sonrası FT4, TSH, antiTPO, antiTG, PTH ve ALP seviyeleri açısından arada istatistiksel olarak anlamlı fark vardı (p<0.05). D vitamini tedavi sonrasında 25 (OH) D3 ve FT4 seviyelerinde istatiksel olarak önemli bir artış olurken TSH, antiTPO, antiTG, PTH ve ALP seviyelerinde ise önemli bir düşüş gözlendi. FT3, Ca, P, TNF-α, IL-6 ve IL-1b açısından önemli bir fark yoktu. D vitamini seviyesi ile FT3, FT4, TSH, antiTPO, antiTG, TNF-α, IL-6 ve IL-1b arasında bir korelasyon yoktu. Sonuç: D vitamini eksikliği ve yeni tanı HT'i olan hastalarda D vitamini tedavisinin tiroid antijenitesi ve tiroid fonksiyonu üzerine olumlu yönde etkisi vardır.

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TRAIL Death Pathway Expression and Induction in Thyroid Follicular Cells

Cited by 78 publications

References 47 publications

TRAIL-induced apoptosis of thyroid cancer cells: potential for therapeutic intervention

TRAIL-induced apoptosis of thyroid cancer cells: potential for therapeutic intervention

TNF-Related Apoptosis-Inducing Ligand Death Pathway-Mediated Human Beta-Cell Destruction

The effect of Vitamin D treatment on thyroid function and the levels of thyroid autoantibodies, TNF-α, IL-6, IL-1β in patients with autoimmune thyroiditis

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