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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356111/ https://www.ncbi.nlm.nih.gov/pubmed/22654792 http://dx.doi.org/10.3389/fendo.2011.00010 |
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author | Carvalho-Sousa, Claudia Emanuele da Silveira Cruz-Machado, Sanseray Tamura, Eduardo Koji Fernandes, Pedro A. C. M. Pinato, Luciana Muxel, Sandra M. Cecon, Erika Markus, Regina P. |
author_facet | Carvalho-Sousa, Claudia Emanuele da Silveira Cruz-Machado, Sanseray Tamura, Eduardo Koji Fernandes, Pedro A. C. M. Pinato, Luciana Muxel, Sandra M. Cecon, Erika Markus, Regina P. |
author_sort | Carvalho-Sousa, Claudia Emanuele |
collection | PubMed |
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 of TNF and reinforce the idea that the suppression of pineal melatonin is one of the mechanisms involved in mounting an innate immune response. |
format | Online Article Text |
id | pubmed-3356111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33561112012-05-31 Molecular Basis for Defining the Pineal Gland and Pinealocytes as Targets for Tumor Necrosis Factor Carvalho-Sousa, Claudia Emanuele da Silveira Cruz-Machado, Sanseray Tamura, Eduardo Koji Fernandes, Pedro A. C. M. Pinato, Luciana Muxel, Sandra M. Cecon, Erika Markus, Regina P. Front Endocrinol (Lausanne) Endocrinology 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 of TNF and reinforce the idea that the suppression of pineal melatonin is one of the mechanisms involved in mounting an innate immune response. Frontiers Research Foundation 2011-05-13 /pmc/articles/PMC3356111/ /pubmed/22654792 http://dx.doi.org/10.3389/fendo.2011.00010 Text en Copyright © 2011 Carvalho-Sousa, da Silveira Cruz-Machado, Tamura, Fernandes, Pinato, Muxel, Cecon and Markus. http://www.frontiersin.org/licenseagreement This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with. |
spellingShingle | Endocrinology Carvalho-Sousa, Claudia Emanuele da Silveira Cruz-Machado, Sanseray Tamura, Eduardo Koji Fernandes, Pedro A. C. M. Pinato, Luciana Muxel, Sandra M. Cecon, Erika Markus, Regina P. 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 |
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_short | 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 |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356111/ https://www.ncbi.nlm.nih.gov/pubmed/22654792 http://dx.doi.org/10.3389/fendo.2011.00010 |
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