TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells

Detalhes bibliográficos
Autor(a) principal: Faria, Márcia
Data de Publicação: 2020
Outros Autores: Domingues, Rita, Paixão, Francisca, Bugalho, Maria João, Matos, Paulo, Silva, Ana Luísa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/41838
Resumo: © 2020 Faria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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spelling TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells© 2020 Faria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The sodium-iodide symporter (NIS) mediates transport of iodide across the basolateral membrane of thyroid cells. NIS expression in thyroid cancer (TC) cells allows the use of radioactive iodine (RAI) as a diagnostic and therapeutic tool, being RAI therapy the systemic treatment of choice for metastatic disease. Still, a significant proportion of patients with advanced TC lose the ability to respond to RAI therapy and no effective alternative therapies are available. Defective NIS expression is the main reason for impaired iodide uptake in TC and NIS downregulation has been associated with several pathways linked to malignant transformation. NF-κB signaling is one of the pathways associated with TC. Interestingly, NIS expression can be negatively regulated by TNF-α, a bona fide activator of NF-κB with a central role in thyroid autoimmunity. This prompted us to clarify NF-kB’s role in this process. We confirmed that TNF-α leads to downregulation of TSH-induced NIS expression in non-neoplastic thyroid follicular cell-derived models. Notably, a similar effect was observed when NF-κB activation was triggered independently of ligand-receptor specificity, using phorbol-myristate-acetate (PMA). TNF-α and PMA downregulation of NIS expression was reverted when NF-κB-dependent transcription was blocked, demonstrating the requirement for NF-kB activity. Additionally, TNF-α and PMA were shown to have a negative impact on TSH-induced iodide uptake, consistent with the observed transcriptional downregulation of NIS. Our data support the involvement of NF-κB-directed transcription in the modulation of NIS expression, where up- or down-regulation of NIS depends on the combined output to NF-κB of several converging pathways. A better understanding of the mechanisms underlying NIS expression in the context of normal thyroid physiology may guide the development of pharmacological strategies to increase the efficiency of iodide uptake. Such strategies would be extremely useful in improving the response to RAI therapy in refractory-TC.This work was supported by the Fundação para a Ciência e a Tecnologia, grant [PTDC/BIAMOL/31787/2017] from Portugal. MF is recipient of FCT fellowship PD/BD/114388/2016.PLoSRepositório da Universidade de LisboaFaria, MárciaDomingues, RitaPaixão, FranciscaBugalho, Maria JoãoMatos, PauloSilva, Ana Luísa2020-02-14T15:15:13Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/41838engPLoS ONE 15(2): e0228794.10.1371/journal.pone.02287941932-6203info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:41:27Zoai:repositorio.ul.pt:10451/41838Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:55:01.977875Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
title TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
spellingShingle TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
Faria, Márcia
title_short TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
title_full TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
title_fullStr TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
title_full_unstemmed TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
title_sort TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells
author Faria, Márcia
author_facet Faria, Márcia
Domingues, Rita
Paixão, Francisca
Bugalho, Maria João
Matos, Paulo
Silva, Ana Luísa
author_role author
author2 Domingues, Rita
Paixão, Francisca
Bugalho, Maria João
Matos, Paulo
Silva, Ana Luísa
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Faria, Márcia
Domingues, Rita
Paixão, Francisca
Bugalho, Maria João
Matos, Paulo
Silva, Ana Luísa
description © 2020 Faria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2020
dc.date.none.fl_str_mv 2020-02-14T15:15:13Z
2020
2020-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/41838
url http://hdl.handle.net/10451/41838
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS ONE 15(2): e0228794.
10.1371/journal.pone.0228794
1932-6203
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLoS
publisher.none.fl_str_mv PLoS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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