The role of nitric oxide synthases in pemphigus vulgaris in a mouse model

Pemphigus vulgaris (PV) is a blistering autoimmune disease characterized by IgG autoantibodies against desmoglein 3. Nitric oxide synthases (NOS) may contribute to the increase of inflammation in tissues by the generation of nitrotyrosine residues (NTR). OBJECTIVES: To investigate whether the produc...

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Autores: Marquina, M. (Miren)|||/items/1977b42d-6aca-4510-801b-4ca2ebfc41b9, España-Alonso, A. (Agustín)|||/items/a6e3549c-ab30-4d2e-90a5-fd108573bc9f, Fernadez-Galar, M. (Marta)|||/items/c85b956a-f96f-46b4-b6ac-ae21408da871, Lopez-Zabalza, M.J. (María Jesús)|||/items/6b8ff4f5-9082-4027-8983-4482e8abdef3
Formato: artículo
Fecha de publicación:2008
País:España
Recursos:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23824
Acesso em linha:https://hdl.handle.net/10171/23824
Access Level:acceso abierto
Palavra-chave:Nitric Oxide Synthase Type I/metabolism
Pemphigus/enzymology
Immunoglobulin G/metabolism
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spelling The role of nitric oxide synthases in pemphigus vulgaris in a mouse modelMarquina, M. (Miren)|||/items/1977b42d-6aca-4510-801b-4ca2ebfc41b9España-Alonso, A. (Agustín)|||/items/a6e3549c-ab30-4d2e-90a5-fd108573bc9fFernadez-Galar, M. (Marta)|||/items/c85b956a-f96f-46b4-b6ac-ae21408da871Lopez-Zabalza, M.J. (María Jesús)|||/items/6b8ff4f5-9082-4027-8983-4482e8abdef3Nitric Oxide Synthase Type I/metabolismPemphigus/enzymologyImmunoglobulin G/metabolismPemphigus vulgaris (PV) is a blistering autoimmune disease characterized by IgG autoantibodies against desmoglein 3. Nitric oxide synthases (NOS) may contribute to the increase of inflammation in tissues by the generation of nitrotyrosine residues (NTR). OBJECTIVES: To investigate whether the production of NTR mediated by NOS may participate in the development of inflammation and acantholysis in PV. METHODS: Mice were pretreated or not with NOS, tyrosine-kinase (TK) or nuclear factor (NF)-kappaB inhibitors, and then injected with PV-IgG. PV manifestations were examined in all mice. The expression of NTR, constitutive NOS (cNOS) [endothelial NOS (eNOS) and neuronal NOS (nNOS)], inducible NOS (iNOS) and NF-kappaB factor were studied in epidermis of mice using immunohistochemical techniques. RESULTS: After PV-IgG injection, expressions of NTR, iNOS, eNOS and nNOS increased in acantholytic cells, as did nuclear translocation of NF-kappaB in the basal cells of the epidermis. Pretreatment of mice with inhibitors of TK, nNOS and nonselective NOS, completely prevented NTR expression and the clinical and histological findings of PV in mice. TK inhibitor genistein inhibited both nNOS and iNOS expression on the membrane of basal keratinocytes, and nuclear translocation of NF-kappaB. CONCLUSIONS: Upregulation of cNOS and iNOS, NTR generation and nuclear translocation of NF-kappaB may contribute to increased inflammation and tissue damage in PV lesions. The absence of the clinical and histological findings of PV and NTR expression in mice injected with PV-IgG, through pretreatment with TK and nNOS inhibitors, provides compelling evidence that these signalling molecules should be considered as potential therapeutic targets in PV.Wiley-BlackwellDadun. Depósito Académico Digital Universidad de Navarra20122012-11-2720082008-01-0120082008-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/23824reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/238242026-06-21T12:47:57Z
dc.title.none.fl_str_mv The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
title The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
spellingShingle The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
Marquina, M. (Miren)|||/items/1977b42d-6aca-4510-801b-4ca2ebfc41b9
Nitric Oxide Synthase Type I/metabolism
Pemphigus/enzymology
Immunoglobulin G/metabolism
title_short The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
title_full The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
title_fullStr The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
title_full_unstemmed The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
title_sort The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
dc.creator.none.fl_str_mv Marquina, M. (Miren)|||/items/1977b42d-6aca-4510-801b-4ca2ebfc41b9
España-Alonso, A. (Agustín)|||/items/a6e3549c-ab30-4d2e-90a5-fd108573bc9f
Fernadez-Galar, M. (Marta)|||/items/c85b956a-f96f-46b4-b6ac-ae21408da871
Lopez-Zabalza, M.J. (María Jesús)|||/items/6b8ff4f5-9082-4027-8983-4482e8abdef3
author Marquina, M. (Miren)|||/items/1977b42d-6aca-4510-801b-4ca2ebfc41b9
author_facet Marquina, M. (Miren)|||/items/1977b42d-6aca-4510-801b-4ca2ebfc41b9
España-Alonso, A. (Agustín)|||/items/a6e3549c-ab30-4d2e-90a5-fd108573bc9f
Fernadez-Galar, M. (Marta)|||/items/c85b956a-f96f-46b4-b6ac-ae21408da871
Lopez-Zabalza, M.J. (María Jesús)|||/items/6b8ff4f5-9082-4027-8983-4482e8abdef3
author_role author
author2 España-Alonso, A. (Agustín)|||/items/a6e3549c-ab30-4d2e-90a5-fd108573bc9f
Fernadez-Galar, M. (Marta)|||/items/c85b956a-f96f-46b4-b6ac-ae21408da871
Lopez-Zabalza, M.J. (María Jesús)|||/items/6b8ff4f5-9082-4027-8983-4482e8abdef3
author2_role author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Nitric Oxide Synthase Type I/metabolism
Pemphigus/enzymology
Immunoglobulin G/metabolism
topic Nitric Oxide Synthase Type I/metabolism
Pemphigus/enzymology
Immunoglobulin G/metabolism
description Pemphigus vulgaris (PV) is a blistering autoimmune disease characterized by IgG autoantibodies against desmoglein 3. Nitric oxide synthases (NOS) may contribute to the increase of inflammation in tissues by the generation of nitrotyrosine residues (NTR). OBJECTIVES: To investigate whether the production of NTR mediated by NOS may participate in the development of inflammation and acantholysis in PV. METHODS: Mice were pretreated or not with NOS, tyrosine-kinase (TK) or nuclear factor (NF)-kappaB inhibitors, and then injected with PV-IgG. PV manifestations were examined in all mice. The expression of NTR, constitutive NOS (cNOS) [endothelial NOS (eNOS) and neuronal NOS (nNOS)], inducible NOS (iNOS) and NF-kappaB factor were studied in epidermis of mice using immunohistochemical techniques. RESULTS: After PV-IgG injection, expressions of NTR, iNOS, eNOS and nNOS increased in acantholytic cells, as did nuclear translocation of NF-kappaB in the basal cells of the epidermis. Pretreatment of mice with inhibitors of TK, nNOS and nonselective NOS, completely prevented NTR expression and the clinical and histological findings of PV in mice. TK inhibitor genistein inhibited both nNOS and iNOS expression on the membrane of basal keratinocytes, and nuclear translocation of NF-kappaB. CONCLUSIONS: Upregulation of cNOS and iNOS, NTR generation and nuclear translocation of NF-kappaB may contribute to increased inflammation and tissue damage in PV lesions. The absence of the clinical and histological findings of PV and NTR expression in mice injected with PV-IgG, through pretreatment with TK and nNOS inhibitors, provides compelling evidence that these signalling molecules should be considered as potential therapeutic targets in PV.
publishDate 2008
dc.date.none.fl_str_mv 2008
2008-01-01
2008
2008-01-01
2012
2012-11-27
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/23824
url https://hdl.handle.net/10171/23824
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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