Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UNIFESP |
| Texto Completo: | http://dx.doi.org/10.3389/fnmol.2018.00050 https://repositorio.unifesp.br/handle/11600/55836 |
Resumo: | Chronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEX |
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Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epitheliumanosmiainflammationcorticoidsinnate immune responseneurogenesisneuronal cell deathS6 kinaseToll-like receptor 4Chronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEX200 or 800 ng/nostril), a potent synthetic anti-inflammatory steroid, attenuates OE lesion caused by Gram-negative bacteria lipopolysaccharide (LPS) intranasal infusion. In contrast, repeated DEX (400 ng/nostril) local application after lesion establishment limited the regeneration of olfactory sensory neurons after injury promoted by LPS or methimazole. Remarkably, DEX effects were observed when the drug was infused as 3 consecutive days regimen. The anti-inflammatory drug does not induce OE progenitor cell death, however, disturbance in mammalian target of rapamycin downstream signaling pathway and impairment of protein synthesis were observed during the course of DEX treatment. In addition, in vitro studies conducted with OE neurospheres in the absence of an inflammatory environment showed that glucocorticoid receptor engagement directly reduces OE progenitor cells proliferation. Our results suggest that DEX can interfere with the intrinsic regenerative cellular mechanisms of the OE, raising concerns on the use of topical anti-inflammatory steroids as a risk factor for progressive olfactory function impairment.Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo, BrazilUniv Sao Paulo, Inst Quim, Dept Biochem, Sao Paulo, BrazilUniv Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo, BrazilUniv Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilWeb of ScienceFundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESPConselho Nacional de Desenvolvimento Cientifico e TecnologicoCEPID RedoxomaFAPESP: 2007/53732-8FAPESP: 2013/07937-8FAPESP: 2011/13134-0FAPESP: 2009/04437-9FAPESP: 2016/24471-0FAPESP: 2009/52047-5FAPESP: 2010/50023-9CNPq: 484869/2012-4CNPq: 309860/2011-3CNPq: 478903/2012-0Frontiers Media Sa2020-07-20T16:31:16Z2020-07-20T16:31:16Z2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.3389/fnmol.2018.00050Frontiers In Molecular Neuroscience. Lausanne, v. 11, p. -, 2018.10.3389/fnmol.2018.00050WOS000426748200001.pdf1662-5099https://repositorio.unifesp.br/handle/11600/55836WOS:000426748200001engFrontiers In Molecular NeuroscienceLausanneinfo:eu-repo/semantics/openAccessCrisafulli, Umberto [UNIFESP]Xavier, Andre Machado [UNIFESP]Santos, Fabiana B. dos [UNIFESP]Cambiaghi, Tavane David [UNIFESP]Chang, Seo Y. [UNIFESP]Porcionatto, Marimélia Aparecida [UNIFESP]Castilho, Beatriz Amaral de [UNIFESP]Malnic, BettinaGlezer, Isaias [UNIFESP]reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-03T08:27:45Zoai:repositorio.unifesp.br/:11600/55836Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-03T08:27:45Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
| dc.title.none.fl_str_mv |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| spellingShingle |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium Crisafulli, Umberto [UNIFESP] anosmia inflammation corticoids innate immune response neurogenesis neuronal cell death S6 kinase Toll-like receptor 4 |
| title_short |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_full |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_fullStr |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_full_unstemmed |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_sort |
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| author |
Crisafulli, Umberto [UNIFESP] |
| author_facet |
Crisafulli, Umberto [UNIFESP] Xavier, Andre Machado [UNIFESP] Santos, Fabiana B. dos [UNIFESP] Cambiaghi, Tavane David [UNIFESP] Chang, Seo Y. [UNIFESP] Porcionatto, Marimélia Aparecida [UNIFESP] Castilho, Beatriz Amaral de [UNIFESP] Malnic, Bettina Glezer, Isaias [UNIFESP] |
| author_role |
author |
| author2 |
Xavier, Andre Machado [UNIFESP] Santos, Fabiana B. dos [UNIFESP] Cambiaghi, Tavane David [UNIFESP] Chang, Seo Y. [UNIFESP] Porcionatto, Marimélia Aparecida [UNIFESP] Castilho, Beatriz Amaral de [UNIFESP] Malnic, Bettina Glezer, Isaias [UNIFESP] |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Crisafulli, Umberto [UNIFESP] Xavier, Andre Machado [UNIFESP] Santos, Fabiana B. dos [UNIFESP] Cambiaghi, Tavane David [UNIFESP] Chang, Seo Y. [UNIFESP] Porcionatto, Marimélia Aparecida [UNIFESP] Castilho, Beatriz Amaral de [UNIFESP] Malnic, Bettina Glezer, Isaias [UNIFESP] |
| dc.subject.por.fl_str_mv |
anosmia inflammation corticoids innate immune response neurogenesis neuronal cell death S6 kinase Toll-like receptor 4 |
| topic |
anosmia inflammation corticoids innate immune response neurogenesis neuronal cell death S6 kinase Toll-like receptor 4 |
| description |
Chronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEX |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2020-07-20T16:31:16Z 2020-07-20T16:31:16Z |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fnmol.2018.00050 Frontiers In Molecular Neuroscience. Lausanne, v. 11, p. -, 2018. 10.3389/fnmol.2018.00050 WOS000426748200001.pdf 1662-5099 https://repositorio.unifesp.br/handle/11600/55836 WOS:000426748200001 |
| url |
http://dx.doi.org/10.3389/fnmol.2018.00050 https://repositorio.unifesp.br/handle/11600/55836 |
| identifier_str_mv |
Frontiers In Molecular Neuroscience. Lausanne, v. 11, p. -, 2018. 10.3389/fnmol.2018.00050 WOS000426748200001.pdf 1662-5099 WOS:000426748200001 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Frontiers In Molecular Neuroscience |
| 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.coverage.none.fl_str_mv |
Lausanne |
| dc.publisher.none.fl_str_mv |
Frontiers Media Sa |
| publisher.none.fl_str_mv |
Frontiers Media Sa |
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reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
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biblioteca.csp@unifesp.br |
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1814268343068131328 |