Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor

The pineal gland, the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, sup...

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Autores: Carvalho-Sousa, Claudia Emanuele, da Silveira Cruz-Machado, Sanseray, Tamura, Koji Eduardo, Fernandes, Pedro A.C.M., Pinato, Luciana [UNESP], Muxel, Sandra M., Cecon, Erika, Markus, Regina P.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/72097
Acceso en línea:http://dx.doi.org/10.3389/fendo.2011.00010
http://hdl.handle.net/11449/72097
Access Level:acceso abierto
Palabra clave:Immune-pineal axis
Melatonin
Nuclear factor kappa B
Pineal gland
Tumor necrosis factor
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spelling Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factorImmune-pineal axisMelatoninNuclear factor kappa BPineal glandTumor necrosis factorThe pineal gland, the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, suppresses the translation of the key enzyme of melatonin synthesis (arylalkylamine-N-acetyltransferase, Aanat). Here, we show that TNF receptors of the subtype 1 (TNF-R1) are expressed by astrocytes, microglia, and pinealocytes. We also show that the TNF signaling reduces the level of inhibitory nuclear factor kappa B protein subtype A (NFKBIA), leading to the nuclear translocation of two NFKB dimers, p50/p50, and p50/RelA. The lack of a transactivating domain in the p50/p50 dimer suggests that this dimer is responsible for the repression of Aanat transcription. Meanwhile, p50/RelA promotes the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide, which inhibits adrenergically induced melatonin production. Together, these data provide a mechanistic basis for considering pinealocytes a target ofTNF and reinforce the idea that the suppression of pineal melatonin is one of the mechanisms involved in mounting an innate immune response. © 2011 Carvalho-Sousa, da Silveira Cruz-Machado, Tamura, Fernandes, Pinato, Muxel, Cecon and Markus.Laboratory of Chronopharmacology Department of Physiology Institute of Biosciences, Universidade de São Paulo, São PauloDepartment of Speech, Language and Hearing Therapy Universidade Estadual Paulista, MaríliaDepartment of Speech, Language and Hearing Therapy Universidade Estadual Paulista, MaríliaUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)2014-05-27T11:25:22Z2014-05-27T11:25:22Z2010-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.3389/fendo.2011.00010Frontiers in Endocrinology, v. 2, n. MAY, 2010.1664-2392http://hdl.handle.net/11449/7209710.3389/fendo.2011.000102-s2.0-848741456652-s2.0-84874145665.pdf8372363591179624Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Endocrinology3.5191,790info:eu-repo/semantics/openAccessCarvalho-Sousa, Claudia Emanueleda Silveira Cruz-Machado, SanserayTamura, Koji EduardoFernandes, Pedro A.C.M.Pinato, Luciana [UNESP]Muxel, Sandra M.Cecon, ErikaMarkus, Regina P.2024-08-09T17:39:02Zoai:repositorio.unesp.br:11449/72097Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-08-09T17:39:02Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
title Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
spellingShingle Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
Carvalho-Sousa, Claudia Emanuele
Immune-pineal axis
Melatonin
Nuclear factor kappa B
Pineal gland
Tumor necrosis factor
title_short Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
title_full Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
title_fullStr Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
title_full_unstemmed Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
title_sort Molecular basis for defining the pineal gland and pinealocytes as targets for tumor necrosis factor
dc.creator.none.fl_str_mv Carvalho-Sousa, Claudia Emanuele
da Silveira Cruz-Machado, Sanseray
Tamura, Koji Eduardo
Fernandes, Pedro A.C.M.
Pinato, Luciana [UNESP]
Muxel, Sandra M.
Cecon, Erika
Markus, Regina P.
author Carvalho-Sousa, Claudia Emanuele
author_facet Carvalho-Sousa, Claudia Emanuele
da Silveira Cruz-Machado, Sanseray
Tamura, Koji Eduardo
Fernandes, Pedro A.C.M.
Pinato, Luciana [UNESP]
Muxel, Sandra M.
Cecon, Erika
Markus, Regina P.
author_role author
author2 da Silveira Cruz-Machado, Sanseray
Tamura, Koji Eduardo
Fernandes, Pedro A.C.M.
Pinato, Luciana [UNESP]
Muxel, Sandra M.
Cecon, Erika
Markus, Regina P.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
dc.subject.por.fl_str_mv Immune-pineal axis
Melatonin
Nuclear factor kappa B
Pineal gland
Tumor necrosis factor
topic Immune-pineal axis
Melatonin
Nuclear factor kappa B
Pineal gland
Tumor necrosis factor
description The pineal gland, the gland that translates darkness into an endocrine signal by releasing melatonin at night, is now considered a key player in the mounting of an innate immune response. Tumor necrosis factor (TNF), the first pro-inflammatory cytokine to be released by an inflammatory response, suppresses the translation of the key enzyme of melatonin synthesis (arylalkylamine-N-acetyltransferase, Aanat). Here, we show that TNF receptors of the subtype 1 (TNF-R1) are expressed by astrocytes, microglia, and pinealocytes. We also show that the TNF signaling reduces the level of inhibitory nuclear factor kappa B protein subtype A (NFKBIA), leading to the nuclear translocation of two NFKB dimers, p50/p50, and p50/RelA. The lack of a transactivating domain in the p50/p50 dimer suggests that this dimer is responsible for the repression of Aanat transcription. Meanwhile, p50/RelA promotes the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide, which inhibits adrenergically induced melatonin production. Together, these data provide a mechanistic basis for considering pinealocytes a target ofTNF and reinforce the idea that the suppression of pineal melatonin is one of the mechanisms involved in mounting an innate immune response. © 2011 Carvalho-Sousa, da Silveira Cruz-Machado, Tamura, Fernandes, Pinato, Muxel, Cecon and Markus.
publishDate 2010
dc.date.none.fl_str_mv 2010-12-01
2014-05-27T11:25:22Z
2014-05-27T11:25:22Z
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://dx.doi.org/10.3389/fendo.2011.00010
Frontiers in Endocrinology, v. 2, n. MAY, 2010.
1664-2392
http://hdl.handle.net/11449/72097
10.3389/fendo.2011.00010
2-s2.0-84874145665
2-s2.0-84874145665.pdf
8372363591179624
url http://dx.doi.org/10.3389/fendo.2011.00010
http://hdl.handle.net/11449/72097
identifier_str_mv Frontiers in Endocrinology, v. 2, n. MAY, 2010.
1664-2392
10.3389/fendo.2011.00010
2-s2.0-84874145665
2-s2.0-84874145665.pdf
8372363591179624
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Endocrinology
3.519
1,790
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.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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score 15,300724

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