Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.meegid.2018.12.033 http://hdl.handle.net/11449/185487 |
Resumo: | Clinical manifestations of dengue disease rely on complex interactions between dengue virus (DENV) and host factors that drive altered immune responses, including excessive inflammation. We have recently established that vitamin D can modulate DENV-induced cytokine responses and restrict infection in human macrophages. Cytokine responses are finely regulated by several homeostatic mechanisms, including microRNAs (miRNAs) that can rapidly target specific genes involved in the control of immune signaling pathways. However, the modulation of miRNAs by vitamin D during DENV infection is still unknown. Here, using a qPCR miRNA array we profiled immune-related miRNAs induced by DENV infection in human monocyte-derived macrophages (MDM) differentiated in absence or presence of vitamin D (D3-MDM). We found several miRNAs differentially expressed in both MDM and D3-MDM upon DENV infection. Interestingly, from these, a set of 11 miRNAs were attenuated in D3-MDM as compared to MDM. Gene set enrichment analysis of the predicted mRNA targets of these attenuated miRNAs suggested a predominant role of miR-155-5p in the TLR-induced cytokine responses. Indeed, validation of miR-155-5p attenuation in D3-MDM was linked to increased expression of its target gene SOCS-1, a key component for TLR4 signaling regulation. Likewise, TLR4 activation with LPS further corroborated the same miR-155-5p/SOCS-1 negative correlation observed in D3-MDM upon DENV exposure. Moreover, D3-MDM differentiation induced down-regulation of surface TLR4 that was linked to less TLR4/NF-kappa B-derived secretion of IL-1 beta. These data suggest a key role of vitamin D in the control of inflammatory cytokine responses during DENV infection of human macrophages via the TLR4/NF-kappa B/miR-155-5p/SOCS-1 axis. |
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Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine responseVitamin DmiRNA-155TLR4ImmunomodulationDengue virusCytokine responseClinical manifestations of dengue disease rely on complex interactions between dengue virus (DENV) and host factors that drive altered immune responses, including excessive inflammation. We have recently established that vitamin D can modulate DENV-induced cytokine responses and restrict infection in human macrophages. Cytokine responses are finely regulated by several homeostatic mechanisms, including microRNAs (miRNAs) that can rapidly target specific genes involved in the control of immune signaling pathways. However, the modulation of miRNAs by vitamin D during DENV infection is still unknown. Here, using a qPCR miRNA array we profiled immune-related miRNAs induced by DENV infection in human monocyte-derived macrophages (MDM) differentiated in absence or presence of vitamin D (D3-MDM). We found several miRNAs differentially expressed in both MDM and D3-MDM upon DENV infection. Interestingly, from these, a set of 11 miRNAs were attenuated in D3-MDM as compared to MDM. Gene set enrichment analysis of the predicted mRNA targets of these attenuated miRNAs suggested a predominant role of miR-155-5p in the TLR-induced cytokine responses. Indeed, validation of miR-155-5p attenuation in D3-MDM was linked to increased expression of its target gene SOCS-1, a key component for TLR4 signaling regulation. Likewise, TLR4 activation with LPS further corroborated the same miR-155-5p/SOCS-1 negative correlation observed in D3-MDM upon DENV exposure. Moreover, D3-MDM differentiation induced down-regulation of surface TLR4 that was linked to less TLR4/NF-kappa B-derived secretion of IL-1 beta. These data suggest a key role of vitamin D in the control of inflammatory cytokine responses during DENV infection of human macrophages via the TLR4/NF-kappa B/miR-155-5p/SOCS-1 axis.COLCIENCIAS from ColombiaCODI, Universidad de Antioquia, UdeAUniv Antioquia, UdeA, Fac Med, Grp Inmunovirol, Calle 70 52-21, Medellin, ColombiaSao Paulo State Univ, Dept Morphol, BR-18618689 Botucatu, SP, BrazilSao Paulo State Univ, Dept Morphol, BR-18618689 Botucatu, SP, BrazilCOLCIENCIAS from Colombia: 111556933443CODI, Universidad de Antioquia, UdeA: 2015-7803Elsevier B.V.Univ AntioquiaUniversidade Estadual Paulista (Unesp)Arboleda, John F.Fernandez, Geysson J. [UNESP]Urcuqui-Inchima, Silvio2019-10-04T12:35:56Z2019-10-04T12:35:56Z2019-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12-21http://dx.doi.org/10.1016/j.meegid.2018.12.033Infection Genetics And Evolution. Amsterdam: Elsevier Science Bv, v. 69, p. 12-21, 2019.1567-1348http://hdl.handle.net/11449/18548710.1016/j.meegid.2018.12.033WOS:000459932000003Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInfection Genetics And Evolutioninfo:eu-repo/semantics/openAccess2021-10-23T05:17:32Zoai:repositorio.unesp.br:11449/185487Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-06T00:05:02.140913Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
title |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
spellingShingle |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response Arboleda, John F. Vitamin D miRNA-155 TLR4 Immunomodulation Dengue virus Cytokine response |
title_short |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
title_full |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
title_fullStr |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
title_full_unstemmed |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
title_sort |
Vitamin D-mediated attenuation of miR-155 in human macrophages infected with dengue virus: Implications for the cytokine response |
author |
Arboleda, John F. |
author_facet |
Arboleda, John F. Fernandez, Geysson J. [UNESP] Urcuqui-Inchima, Silvio |
author_role |
author |
author2 |
Fernandez, Geysson J. [UNESP] Urcuqui-Inchima, Silvio |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Univ Antioquia Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Arboleda, John F. Fernandez, Geysson J. [UNESP] Urcuqui-Inchima, Silvio |
dc.subject.por.fl_str_mv |
Vitamin D miRNA-155 TLR4 Immunomodulation Dengue virus Cytokine response |
topic |
Vitamin D miRNA-155 TLR4 Immunomodulation Dengue virus Cytokine response |
description |
Clinical manifestations of dengue disease rely on complex interactions between dengue virus (DENV) and host factors that drive altered immune responses, including excessive inflammation. We have recently established that vitamin D can modulate DENV-induced cytokine responses and restrict infection in human macrophages. Cytokine responses are finely regulated by several homeostatic mechanisms, including microRNAs (miRNAs) that can rapidly target specific genes involved in the control of immune signaling pathways. However, the modulation of miRNAs by vitamin D during DENV infection is still unknown. Here, using a qPCR miRNA array we profiled immune-related miRNAs induced by DENV infection in human monocyte-derived macrophages (MDM) differentiated in absence or presence of vitamin D (D3-MDM). We found several miRNAs differentially expressed in both MDM and D3-MDM upon DENV infection. Interestingly, from these, a set of 11 miRNAs were attenuated in D3-MDM as compared to MDM. Gene set enrichment analysis of the predicted mRNA targets of these attenuated miRNAs suggested a predominant role of miR-155-5p in the TLR-induced cytokine responses. Indeed, validation of miR-155-5p attenuation in D3-MDM was linked to increased expression of its target gene SOCS-1, a key component for TLR4 signaling regulation. Likewise, TLR4 activation with LPS further corroborated the same miR-155-5p/SOCS-1 negative correlation observed in D3-MDM upon DENV exposure. Moreover, D3-MDM differentiation induced down-regulation of surface TLR4 that was linked to less TLR4/NF-kappa B-derived secretion of IL-1 beta. These data suggest a key role of vitamin D in the control of inflammatory cytokine responses during DENV infection of human macrophages via the TLR4/NF-kappa B/miR-155-5p/SOCS-1 axis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-04T12:35:56Z 2019-10-04T12:35:56Z 2019-04-01 |
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/10.1016/j.meegid.2018.12.033 Infection Genetics And Evolution. Amsterdam: Elsevier Science Bv, v. 69, p. 12-21, 2019. 1567-1348 http://hdl.handle.net/11449/185487 10.1016/j.meegid.2018.12.033 WOS:000459932000003 |
url |
http://dx.doi.org/10.1016/j.meegid.2018.12.033 http://hdl.handle.net/11449/185487 |
identifier_str_mv |
Infection Genetics And Evolution. Amsterdam: Elsevier Science Bv, v. 69, p. 12-21, 2019. 1567-1348 10.1016/j.meegid.2018.12.033 WOS:000459932000003 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Infection Genetics And Evolution |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
12-21 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science 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 |
|
_version_ |
1808129581364805632 |