Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/38903 http://dx.doi.org/10.1371/journal.pone.0120441 |
Resumo: | Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-alpha and IL-4 content, but not IL-6, IL-13 and IL-10 quantified by ELISA. Mice with decreased levels of VAChT presented increased collagen and elastic fibers deposition in airway walls which was consistent with an increase in inflammatory cells positive to MMP-9 and TIMP-1 in the lung. in vivo lung function evaluation showed airway hyperresponsiveness to methacholine in mutant mice. the expression of nuclear factor-kappa B (p65-NF-kappa B) in lung of VAChT-deficient mice were higher than in wild-type mice, whereas a decreased expression of janus-kinase 2 (JAK2) was observed in the lung of mutant animals. Our findings show the first evidence that cholinergic deficiency impaired lung function and produce local inflammation. Our data supports the notion that cholinergic system modulates airway inflammation by modulation of JAK2 and NF-kappa B pathway. We proposed that intact cholinergic pathway is necessary to maintain the lung homeostasis. |
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Pinheiro, Nathalia M.Miranda, Claudia J. C. P.Perini, AdenirCâmara, Niels Olsen Saraiva [UNIFESP]Costa, Soraia K. P.Alonso-Vale, Maria Isabel C. [UNIFESP]Caperuto, Luciana C. [UNIFESP]Tiberio, Iolanda F. L. C.Prado, Marco Antonio M.Martins, Milton A.Prado, Vania F.Prado, Carla Máximo [UNIFESP]Universidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Univ Western Ontario2016-01-24T14:40:16Z2016-01-24T14:40:16Z2015-03-27Plos One. San Francisco: Public Library Science, v. 10, n. 3, 22 p., 2015.1932-6203http://repositorio.unifesp.br/handle/11600/38903http://dx.doi.org/10.1371/journal.pone.0120441WOS000352133600036.pdf10.1371/journal.pone.0120441WOS:000352133600036Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-alpha and IL-4 content, but not IL-6, IL-13 and IL-10 quantified by ELISA. Mice with decreased levels of VAChT presented increased collagen and elastic fibers deposition in airway walls which was consistent with an increase in inflammatory cells positive to MMP-9 and TIMP-1 in the lung. in vivo lung function evaluation showed airway hyperresponsiveness to methacholine in mutant mice. the expression of nuclear factor-kappa B (p65-NF-kappa B) in lung of VAChT-deficient mice were higher than in wild-type mice, whereas a decreased expression of janus-kinase 2 (JAK2) was observed in the lung of mutant animals. Our findings show the first evidence that cholinergic deficiency impaired lung function and produce local inflammation. Our data supports the notion that cholinergic system modulates airway inflammation by modulation of JAK2 and NF-kappa B pathway. We proposed that intact cholinergic pathway is necessary to maintain the lung homeostasis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Sch Med, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, BrazilUniv São Paulo, Dept Immunol, Inst Biomed Sci, São Paulo, BrazilUniv São Paulo, Dept Pharmacol, Inst Biomed Sci, São Paulo, BrazilUniv Western Ontario, Dept Physiol & Pharmacol, Robarts Res Inst, Mol Med Grp, London, ON, CanadaUniv Western Ontario, Dept Anat & Cell Biol, London, ON, CanadaUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, BrazilFAPESP: FAPESP-2008/55359-5CNPq: 471224/2009-0Web of Science22engPublic Library SciencePlos OnePulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporterinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000352133600036.pdfapplication/pdf3805488${dspace.ui.url}/bitstream/11600/38903/1/WOS000352133600036.pdff9b8143563aa429677ccdb6ef9cf77f4MD51open accessTEXTWOS000352133600036.pdf.txtWOS000352133600036.pdf.txtExtracted texttext/plain59637${dspace.ui.url}/bitstream/11600/38903/9/WOS000352133600036.pdf.txtd827a4c78e950cc7e3f0a7ca85061f95MD59open accessTHUMBNAILWOS000352133600036.pdf.jpgWOS000352133600036.pdf.jpgIM Thumbnailimage/jpeg7506${dspace.ui.url}/bitstream/11600/38903/11/WOS000352133600036.pdf.jpg0b21edf98e74124714aa46ad81bc3b07MD511open access11600/389032023-06-05 19:22:28.01open accessoai:repositorio.unifesp.br:11600/38903Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:22:28Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
title |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
spellingShingle |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter Pinheiro, Nathalia M. |
title_short |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
title_full |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
title_fullStr |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
title_full_unstemmed |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
title_sort |
Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter |
author |
Pinheiro, Nathalia M. |
author_facet |
Pinheiro, Nathalia M. Miranda, Claudia J. C. P. Perini, Adenir Câmara, Niels Olsen Saraiva [UNIFESP] Costa, Soraia K. P. Alonso-Vale, Maria Isabel C. [UNIFESP] Caperuto, Luciana C. [UNIFESP] Tiberio, Iolanda F. L. C. Prado, Marco Antonio M. Martins, Milton A. Prado, Vania F. Prado, Carla Máximo [UNIFESP] |
author_role |
author |
author2 |
Miranda, Claudia J. C. P. Perini, Adenir Câmara, Niels Olsen Saraiva [UNIFESP] Costa, Soraia K. P. Alonso-Vale, Maria Isabel C. [UNIFESP] Caperuto, Luciana C. [UNIFESP] Tiberio, Iolanda F. L. C. Prado, Marco Antonio M. Martins, Milton A. Prado, Vania F. Prado, Carla Máximo [UNIFESP] |
author2_role |
author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) Univ Western Ontario |
dc.contributor.author.fl_str_mv |
Pinheiro, Nathalia M. Miranda, Claudia J. C. P. Perini, Adenir Câmara, Niels Olsen Saraiva [UNIFESP] Costa, Soraia K. P. Alonso-Vale, Maria Isabel C. [UNIFESP] Caperuto, Luciana C. [UNIFESP] Tiberio, Iolanda F. L. C. Prado, Marco Antonio M. Martins, Milton A. Prado, Vania F. Prado, Carla Máximo [UNIFESP] |
description |
Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-alpha and IL-4 content, but not IL-6, IL-13 and IL-10 quantified by ELISA. Mice with decreased levels of VAChT presented increased collagen and elastic fibers deposition in airway walls which was consistent with an increase in inflammatory cells positive to MMP-9 and TIMP-1 in the lung. in vivo lung function evaluation showed airway hyperresponsiveness to methacholine in mutant mice. the expression of nuclear factor-kappa B (p65-NF-kappa B) in lung of VAChT-deficient mice were higher than in wild-type mice, whereas a decreased expression of janus-kinase 2 (JAK2) was observed in the lung of mutant animals. Our findings show the first evidence that cholinergic deficiency impaired lung function and produce local inflammation. Our data supports the notion that cholinergic system modulates airway inflammation by modulation of JAK2 and NF-kappa B pathway. We proposed that intact cholinergic pathway is necessary to maintain the lung homeostasis. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-03-27 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:40:16Z |
dc.date.available.fl_str_mv |
2016-01-24T14:40:16Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 10, n. 3, 22 p., 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/38903 http://dx.doi.org/10.1371/journal.pone.0120441 |
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1932-6203 |
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WOS000352133600036.pdf |
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10.1371/journal.pone.0120441 |
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WOS:000352133600036 |
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Plos One. San Francisco: Public Library Science, v. 10, n. 3, 22 p., 2015. 1932-6203 WOS000352133600036.pdf 10.1371/journal.pone.0120441 WOS:000352133600036 |
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http://repositorio.unifesp.br/handle/11600/38903 http://dx.doi.org/10.1371/journal.pone.0120441 |
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