Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation

Autores
Nazar, Magalí; Nicola, Juan Pablo; Velez, Maria Laura; Pellizas, Claudia Gabriela; Masini, Ana María
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-κB (NF-κB) in the TPO promoter. Chemical inhibition of NF-κB signaling and site-directed mutagenesis of the identified κB-cis-acting element abolished LPS stimulation. Furthermore, chromatin immunoprecipitation assays confirmed that TPO constitutes a novel NF-κB p65 subunit target gene in response to LPS. Additionally, our results indicate that p65 phosphorylation of serine 536 constitutes an essential step in the p65-dependent, LPS-induced transcriptional expression of TPO. In conclusion, here we demonstrated that LPS increases TPO expression, suggesting a novel mechanism involved in the regulation of a major thyroid autoantigen. Our results provide new insights into the potential effects of infectious processes on thyroid homeostasis. Copyright © 2012 by The Endocrine Society.
Fil: Nazar, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Velez, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Masini, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
Thyroid Peroxidase
Lipopolysaccharide
Nf-Kb
P65
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54805
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/54805
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylationNazar, MagalíNicola, Juan PabloVelez, Maria LauraPellizas, Claudia GabrielaMasini, Ana MaríaThyroid PeroxidaseLipopolysaccharideNf-KbP65https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-κB (NF-κB) in the TPO promoter. Chemical inhibition of NF-κB signaling and site-directed mutagenesis of the identified κB-cis-acting element abolished LPS stimulation. Furthermore, chromatin immunoprecipitation assays confirmed that TPO constitutes a novel NF-κB p65 subunit target gene in response to LPS. Additionally, our results indicate that p65 phosphorylation of serine 536 constitutes an essential step in the p65-dependent, LPS-induced transcriptional expression of TPO. In conclusion, here we demonstrated that LPS increases TPO expression, suggesting a novel mechanism involved in the regulation of a major thyroid autoantigen. Our results provide new insights into the potential effects of infectious processes on thyroid homeostasis. Copyright © 2012 by The Endocrine Society.Fil: Nazar, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Velez, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Masini, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaEndocrine Society2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54805Nazar, Magalí; Nicola, Juan Pablo; Velez, Maria Laura; Pellizas, Claudia Gabriela; Masini, Ana María; Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation; Endocrine Society; Endocrinology; 153; 12; 12-2012; 6114-61250013-7227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/23064013info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2012-1567info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:28:10Zoai:ri.conicet.gov.ar:11336/54805instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:28:10.293CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
title Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
spellingShingle Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
Nazar, Magalí
Thyroid Peroxidase
Lipopolysaccharide
Nf-Kb
P65
title_short Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
title_full Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
title_fullStr Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
title_full_unstemmed Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
title_sort Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation
dc.creator.none.fl_str_mv Nazar, Magalí
Nicola, Juan Pablo
Velez, Maria Laura
Pellizas, Claudia Gabriela
Masini, Ana María
author Nazar, Magalí
author_facet Nazar, Magalí
Nicola, Juan Pablo
Velez, Maria Laura
Pellizas, Claudia Gabriela
Masini, Ana María
author_role author
author2 Nicola, Juan Pablo
Velez, Maria Laura
Pellizas, Claudia Gabriela
Masini, Ana María
author2_role author
author
author
author
dc.subject.none.fl_str_mv Thyroid Peroxidase
Lipopolysaccharide
Nf-Kb
P65
topic Thyroid Peroxidase
Lipopolysaccharide
Nf-Kb
P65
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-κB (NF-κB) in the TPO promoter. Chemical inhibition of NF-κB signaling and site-directed mutagenesis of the identified κB-cis-acting element abolished LPS stimulation. Furthermore, chromatin immunoprecipitation assays confirmed that TPO constitutes a novel NF-κB p65 subunit target gene in response to LPS. Additionally, our results indicate that p65 phosphorylation of serine 536 constitutes an essential step in the p65-dependent, LPS-induced transcriptional expression of TPO. In conclusion, here we demonstrated that LPS increases TPO expression, suggesting a novel mechanism involved in the regulation of a major thyroid autoantigen. Our results provide new insights into the potential effects of infectious processes on thyroid homeostasis. Copyright © 2012 by The Endocrine Society.
Fil: Nazar, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Velez, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Masini, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-κB (NF-κB) in the TPO promoter. Chemical inhibition of NF-κB signaling and site-directed mutagenesis of the identified κB-cis-acting element abolished LPS stimulation. Furthermore, chromatin immunoprecipitation assays confirmed that TPO constitutes a novel NF-κB p65 subunit target gene in response to LPS. Additionally, our results indicate that p65 phosphorylation of serine 536 constitutes an essential step in the p65-dependent, LPS-induced transcriptional expression of TPO. In conclusion, here we demonstrated that LPS increases TPO expression, suggesting a novel mechanism involved in the regulation of a major thyroid autoantigen. Our results provide new insights into the potential effects of infectious processes on thyroid homeostasis. Copyright © 2012 by The Endocrine Society.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54805
Nazar, Magalí; Nicola, Juan Pablo; Velez, Maria Laura; Pellizas, Claudia Gabriela; Masini, Ana María; Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation; Endocrine Society; Endocrinology; 153; 12; 12-2012; 6114-6125
0013-7227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54805
identifier_str_mv Nazar, Magalí; Nicola, Juan Pablo; Velez, Maria Laura; Pellizas, Claudia Gabriela; Masini, Ana María; Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation; Endocrine Society; Endocrinology; 153; 12; 12-2012; 6114-6125
0013-7227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/23064013
info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2012-1567
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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