Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice

Autores
Guzman, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; Giordano, Mirta Nilda; Galletti, Jeremías Gastón
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose.: To evaluate the role of nuclear factor–κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Methods.: Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor–κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Results.: Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB–dependent fashion after interaction with T cells. Conclusions.: Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis.
Fil: Guzman, Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gabelloni, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
CONJUNCTIVAL-TOLERANCE
BENZALKONIUM-CHLORIDE
ALLERGIC-CONJUNCTIVITIS
NF-kB
CONJUNTCTIVAL-EPITHELIUM
PRESERVATIVE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/36349
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/36349
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in MiceGuzman, MauricioSabbione, FlorenciaGabelloni, María LauraVanzulli, SilviaTrevani, Analía SilvinaGiordano, Mirta NildaGalletti, Jeremías GastónCONJUNCTIVAL-TOLERANCEBENZALKONIUM-CHLORIDEALLERGIC-CONJUNCTIVITISNF-kBCONJUNTCTIVAL-EPITHELIUMPRESERVATIVEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose.: To evaluate the role of nuclear factor–κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Methods.: Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor–κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Results.: Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB–dependent fashion after interaction with T cells. Conclusions.: Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis.Fil: Guzman, Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gabelloni, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaAssociation for Research in Vision and Ophthalmology2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36349Guzman, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; et al.; Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice; Association for Research in Vision and Ophthalmology; Investigative Ophtalmology & Visual Science; 55; 9; 9-2014; 6116-61261552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.14-14075info:eu-repo/semantics/altIdentifier/url/http://iovs.arvojournals.org/article.aspx?articleid=2166786info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:20Zoai:ri.conicet.gov.ar:11336/36349instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:36:21.143CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
title Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
spellingShingle Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
Guzman, Mauricio
CONJUNCTIVAL-TOLERANCE
BENZALKONIUM-CHLORIDE
ALLERGIC-CONJUNCTIVITIS
NF-kB
CONJUNTCTIVAL-EPITHELIUM
PRESERVATIVE
title_short Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
title_full Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
title_fullStr Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
title_full_unstemmed Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
title_sort Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice
dc.creator.none.fl_str_mv Guzman, Mauricio
Sabbione, Florencia
Gabelloni, María Laura
Vanzulli, Silvia
Trevani, Analía Silvina
Giordano, Mirta Nilda
Galletti, Jeremías Gastón
author Guzman, Mauricio
author_facet Guzman, Mauricio
Sabbione, Florencia
Gabelloni, María Laura
Vanzulli, Silvia
Trevani, Analía Silvina
Giordano, Mirta Nilda
Galletti, Jeremías Gastón
author_role author
author2 Sabbione, Florencia
Gabelloni, María Laura
Vanzulli, Silvia
Trevani, Analía Silvina
Giordano, Mirta Nilda
Galletti, Jeremías Gastón
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CONJUNCTIVAL-TOLERANCE
BENZALKONIUM-CHLORIDE
ALLERGIC-CONJUNCTIVITIS
NF-kB
CONJUNTCTIVAL-EPITHELIUM
PRESERVATIVE
topic CONJUNCTIVAL-TOLERANCE
BENZALKONIUM-CHLORIDE
ALLERGIC-CONJUNCTIVITIS
NF-kB
CONJUNTCTIVAL-EPITHELIUM
PRESERVATIVE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose.: To evaluate the role of nuclear factor–κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Methods.: Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor–κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Results.: Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB–dependent fashion after interaction with T cells. Conclusions.: Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis.
Fil: Guzman, Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gabelloni, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Purpose.: To evaluate the role of nuclear factor–κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Methods.: Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor–κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Results.: Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB–dependent fashion after interaction with T cells. Conclusions.: Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/36349
Guzman, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; et al.; Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice; Association for Research in Vision and Ophthalmology; Investigative Ophtalmology & Visual Science; 55; 9; 9-2014; 6116-6126
1552-5783
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36349
identifier_str_mv Guzman, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; et al.; Restoring Conjunctival Tolerance by Topical Nuclear Factor–κB Inhibitors Reduces Preservative-Facilitated Allergic Conjunctivitis in Mice; Association for Research in Vision and Ophthalmology; Investigative Ophtalmology & Visual Science; 55; 9; 9-2014; 6116-6126
1552-5783
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.14-14075
info:eu-repo/semantics/altIdentifier/url/http://iovs.arvojournals.org/article.aspx?articleid=2166786
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Association for Research in Vision and Ophthalmology
publisher.none.fl_str_mv Association for Research in Vision and Ophthalmology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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