Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1177/0394632016678873 http://hdl.handle.net/11449/169531 |
Resumo: | Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11.10) mice. The modulation with L-NAME increased CD86 expression in BMDC, whereas treatment with NOHA increased both CD80 and CD86 expression. Adoptive transfer of either L-NAME- or NOHA-modulated BMDCs to BALB/c mice reduced the plasma levels of ovalbumin-specific antibody as well as proliferation and cytokine secretion in cultures of spleen cells in comparison adoptive transfer of non-modulated DCs. Conversely, transfer of both modulated and non-modulated BMDCs had no effect on immune response of DO11.10 mice. Together, these results show that the treatment with iNOS and Arg inhibitors leads to increased expression of co-stimulatory molecules in DCs, and provides evidences that L-arginine metabolism may be an important therapeutic target for modulating immune responses in inflammatory disorders. |
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Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigenarginaseco-stimulatory moleculescytokinedendritic cell (DC)nitric oxideproliferationDendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11.10) mice. The modulation with L-NAME increased CD86 expression in BMDC, whereas treatment with NOHA increased both CD80 and CD86 expression. Adoptive transfer of either L-NAME- or NOHA-modulated BMDCs to BALB/c mice reduced the plasma levels of ovalbumin-specific antibody as well as proliferation and cytokine secretion in cultures of spleen cells in comparison adoptive transfer of non-modulated DCs. Conversely, transfer of both modulated and non-modulated BMDCs had no effect on immune response of DO11.10 mice. Together, these results show that the treatment with iNOS and Arg inhibitors leads to increased expression of co-stimulatory molecules in DCs, and provides evidences that L-arginine metabolism may be an important therapeutic target for modulating immune responses in inflammatory disorders.Department of Genetics Evolution and Bioagents Institute of Biology University of Campinas UNICAMPDepartment of Biomedical Science Faculty of Americana FAMInstitute of Biosciences Universidade Estadual Paulista UNESPMedical School University of Campinas UNICAMPInstitute of Biosciences Universidade Estadual Paulista UNESPUniversidade Estadual de Campinas (UNICAMP)FAMUniversidade Estadual Paulista (Unesp)Simioni, Patricia U. [UNESP]Fernandes, Luis G.R.Tamashiro, Wirla M.S.C.2018-12-11T16:46:20Z2018-12-11T16:46:20Z2017-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article44-57application/pdfhttp://dx.doi.org/10.1177/0394632016678873International Journal of Immunopathology and Pharmacology, v. 30, n. 1, p. 44-57, 2017.0394-6320http://hdl.handle.net/11449/16953110.1177/03946320166788732-s2.0-850149952902-s2.0-85014995290.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Immunopathology and Pharmacology0,471info:eu-repo/semantics/openAccess2023-12-08T06:16:56Zoai:repositorio.unesp.br:11449/169531Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:44:39.151817Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
title |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
spellingShingle |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen Simioni, Patricia U. [UNESP] arginase co-stimulatory molecules cytokine dendritic cell (DC) nitric oxide proliferation |
title_short |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
title_full |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
title_fullStr |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
title_full_unstemmed |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
title_sort |
Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen |
author |
Simioni, Patricia U. [UNESP] |
author_facet |
Simioni, Patricia U. [UNESP] Fernandes, Luis G.R. Tamashiro, Wirla M.S.C. |
author_role |
author |
author2 |
Fernandes, Luis G.R. Tamashiro, Wirla M.S.C. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) FAM Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Simioni, Patricia U. [UNESP] Fernandes, Luis G.R. Tamashiro, Wirla M.S.C. |
dc.subject.por.fl_str_mv |
arginase co-stimulatory molecules cytokine dendritic cell (DC) nitric oxide proliferation |
topic |
arginase co-stimulatory molecules cytokine dendritic cell (DC) nitric oxide proliferation |
description |
Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11.10) mice. The modulation with L-NAME increased CD86 expression in BMDC, whereas treatment with NOHA increased both CD80 and CD86 expression. Adoptive transfer of either L-NAME- or NOHA-modulated BMDCs to BALB/c mice reduced the plasma levels of ovalbumin-specific antibody as well as proliferation and cytokine secretion in cultures of spleen cells in comparison adoptive transfer of non-modulated DCs. Conversely, transfer of both modulated and non-modulated BMDCs had no effect on immune response of DO11.10 mice. Together, these results show that the treatment with iNOS and Arg inhibitors leads to increased expression of co-stimulatory molecules in DCs, and provides evidences that L-arginine metabolism may be an important therapeutic target for modulating immune responses in inflammatory disorders. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-03-01 2018-12-11T16:46:20Z 2018-12-11T16:46:20Z |
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/10.1177/0394632016678873 International Journal of Immunopathology and Pharmacology, v. 30, n. 1, p. 44-57, 2017. 0394-6320 http://hdl.handle.net/11449/169531 10.1177/0394632016678873 2-s2.0-85014995290 2-s2.0-85014995290.pdf |
url |
http://dx.doi.org/10.1177/0394632016678873 http://hdl.handle.net/11449/169531 |
identifier_str_mv |
International Journal of Immunopathology and Pharmacology, v. 30, n. 1, p. 44-57, 2017. 0394-6320 10.1177/0394632016678873 2-s2.0-85014995290 2-s2.0-85014995290.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Immunopathology and Pharmacology 0,471 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
44-57 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 |
|
_version_ |
1808129112526553088 |