Flagellin delays spontaneous human neutrophil apoptosis
- Autores
- Salamone, G.V.; Petracca, Y.; Bass, J.I.F.; Rumbo, M.; Nahmod, K.A.; Gabelloni, M.L.; Vermeulen, M.E.; Matteo, M.J.; Geffner, J.R.; Trevani, A.S.
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IBα degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-B activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-B activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-B. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria. © 2010 USCAP, Inc All rights reserved.
Fil:Salamone, G.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Gabelloni, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Vermeulen, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Trevani, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. - Fuente
- Lab. Invest. 2010;90(7):1049-1059
- Materia
-
apoptosis
flagellin
neutrophil
2 (2 amino 3 methoxyphenyl)chromone
3 (4 methylphenylsulfonyl) 2 propenenitrile
4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole
caspase 3
flagellin
I kappa B alpha
interleukin 8
mitogen activated protein kinase 1
mitogen activated protein kinase 3
mitogen activated protein kinase p38
phosphatidylinositol 3 kinase
protein kinase B
protein mcl 1
toll like receptor 5
wortmannin
caspase 3
flagellin
immunoglobulin enhancer binding protein
myeloid cell leukemia sequence 1 protein
protein bcl 2
apoptosis
article
bacterium mutant
cell survival
controlled study
cytokine production
enzyme phosphorylation
flow cytometry
fluorescence microscopy
Helicobacter pylori
human
human cell
leukocyte activation
neutrophil
priority journal
protein degradation
protein expression
Salmonella typhimurium
signal transduction
wild type
cell culture
drug effect
enzymology
flagellum
immunology
metabolism
physiology
salmonellosis
Apoptosis
Caspase 3
Cell Survival
Cells, Cultured
Flagella
Flagellin
Humans
MAP Kinase Signaling System
Neutrophils
NF-kappa B
Proto-Oncogene Proteins c-bcl-2
Salmonella Infections
Salmonella typhimurium - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by/2.5/ar
- Repositorio
- Institución
- Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
- OAI Identificador
- paperaa:paper_00236837_v90_n7_p1049_Salamone
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paperaa:paper_00236837_v90_n7_p1049_Salamone |
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Flagellin delays spontaneous human neutrophil apoptosisSalamone, G.V.Petracca, Y.Bass, J.I.F.Rumbo, M.Nahmod, K.A.Gabelloni, M.L.Vermeulen, M.E.Matteo, M.J.Geffner, J.R.Trevani, A.S.apoptosisflagellinneutrophil2 (2 amino 3 methoxyphenyl)chromone3 (4 methylphenylsulfonyl) 2 propenenitrile4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazolecaspase 3flagellinI kappa B alphainterleukin 8mitogen activated protein kinase 1mitogen activated protein kinase 3mitogen activated protein kinase p38phosphatidylinositol 3 kinaseprotein kinase Bprotein mcl 1toll like receptor 5wortmannincaspase 3flagellinimmunoglobulin enhancer binding proteinmyeloid cell leukemia sequence 1 proteinprotein bcl 2apoptosisarticlebacterium mutantcell survivalcontrolled studycytokine productionenzyme phosphorylationflow cytometryfluorescence microscopyHelicobacter pylorihumanhuman cellleukocyte activationneutrophilpriority journalprotein degradationprotein expressionSalmonella typhimuriumsignal transductionwild typecell culturedrug effectenzymologyflagellumimmunologymetabolismphysiologysalmonellosisApoptosisCaspase 3Cell SurvivalCells, CulturedFlagellaFlagellinHumansMAP Kinase Signaling SystemNeutrophilsNF-kappa BProto-Oncogene Proteins c-bcl-2Salmonella InfectionsSalmonella typhimuriumNeutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IBα degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-B activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-B activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-B. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria. © 2010 USCAP, Inc All rights reserved.Fil:Salamone, G.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Gabelloni, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Vermeulen, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Trevani, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_00236837_v90_n7_p1049_SalamoneLab. Invest. 2010;90(7):1049-1059reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-09-29T13:43:00Zpaperaa:paper_00236837_v90_n7_p1049_SalamoneInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-09-29 13:43:01.875Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse |
dc.title.none.fl_str_mv |
Flagellin delays spontaneous human neutrophil apoptosis |
title |
Flagellin delays spontaneous human neutrophil apoptosis |
spellingShingle |
Flagellin delays spontaneous human neutrophil apoptosis Salamone, G.V. apoptosis flagellin neutrophil 2 (2 amino 3 methoxyphenyl)chromone 3 (4 methylphenylsulfonyl) 2 propenenitrile 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole caspase 3 flagellin I kappa B alpha interleukin 8 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B protein mcl 1 toll like receptor 5 wortmannin caspase 3 flagellin immunoglobulin enhancer binding protein myeloid cell leukemia sequence 1 protein protein bcl 2 apoptosis article bacterium mutant cell survival controlled study cytokine production enzyme phosphorylation flow cytometry fluorescence microscopy Helicobacter pylori human human cell leukocyte activation neutrophil priority journal protein degradation protein expression Salmonella typhimurium signal transduction wild type cell culture drug effect enzymology flagellum immunology metabolism physiology salmonellosis Apoptosis Caspase 3 Cell Survival Cells, Cultured Flagella Flagellin Humans MAP Kinase Signaling System Neutrophils NF-kappa B Proto-Oncogene Proteins c-bcl-2 Salmonella Infections Salmonella typhimurium |
title_short |
Flagellin delays spontaneous human neutrophil apoptosis |
title_full |
Flagellin delays spontaneous human neutrophil apoptosis |
title_fullStr |
Flagellin delays spontaneous human neutrophil apoptosis |
title_full_unstemmed |
Flagellin delays spontaneous human neutrophil apoptosis |
title_sort |
Flagellin delays spontaneous human neutrophil apoptosis |
dc.creator.none.fl_str_mv |
Salamone, G.V. Petracca, Y. Bass, J.I.F. Rumbo, M. Nahmod, K.A. Gabelloni, M.L. Vermeulen, M.E. Matteo, M.J. Geffner, J.R. Trevani, A.S. |
author |
Salamone, G.V. |
author_facet |
Salamone, G.V. Petracca, Y. Bass, J.I.F. Rumbo, M. Nahmod, K.A. Gabelloni, M.L. Vermeulen, M.E. Matteo, M.J. Geffner, J.R. Trevani, A.S. |
author_role |
author |
author2 |
Petracca, Y. Bass, J.I.F. Rumbo, M. Nahmod, K.A. Gabelloni, M.L. Vermeulen, M.E. Matteo, M.J. Geffner, J.R. Trevani, A.S. |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
apoptosis flagellin neutrophil 2 (2 amino 3 methoxyphenyl)chromone 3 (4 methylphenylsulfonyl) 2 propenenitrile 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole caspase 3 flagellin I kappa B alpha interleukin 8 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B protein mcl 1 toll like receptor 5 wortmannin caspase 3 flagellin immunoglobulin enhancer binding protein myeloid cell leukemia sequence 1 protein protein bcl 2 apoptosis article bacterium mutant cell survival controlled study cytokine production enzyme phosphorylation flow cytometry fluorescence microscopy Helicobacter pylori human human cell leukocyte activation neutrophil priority journal protein degradation protein expression Salmonella typhimurium signal transduction wild type cell culture drug effect enzymology flagellum immunology metabolism physiology salmonellosis Apoptosis Caspase 3 Cell Survival Cells, Cultured Flagella Flagellin Humans MAP Kinase Signaling System Neutrophils NF-kappa B Proto-Oncogene Proteins c-bcl-2 Salmonella Infections Salmonella typhimurium |
topic |
apoptosis flagellin neutrophil 2 (2 amino 3 methoxyphenyl)chromone 3 (4 methylphenylsulfonyl) 2 propenenitrile 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole caspase 3 flagellin I kappa B alpha interleukin 8 mitogen activated protein kinase 1 mitogen activated protein kinase 3 mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein kinase B protein mcl 1 toll like receptor 5 wortmannin caspase 3 flagellin immunoglobulin enhancer binding protein myeloid cell leukemia sequence 1 protein protein bcl 2 apoptosis article bacterium mutant cell survival controlled study cytokine production enzyme phosphorylation flow cytometry fluorescence microscopy Helicobacter pylori human human cell leukocyte activation neutrophil priority journal protein degradation protein expression Salmonella typhimurium signal transduction wild type cell culture drug effect enzymology flagellum immunology metabolism physiology salmonellosis Apoptosis Caspase 3 Cell Survival Cells, Cultured Flagella Flagellin Humans MAP Kinase Signaling System Neutrophils NF-kappa B Proto-Oncogene Proteins c-bcl-2 Salmonella Infections Salmonella typhimurium |
dc.description.none.fl_txt_mv |
Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IBα degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-B activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-B activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-B. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria. © 2010 USCAP, Inc All rights reserved. Fil:Salamone, G.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gabelloni, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vermeulen, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Trevani, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. |
description |
Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IBα degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-B activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-B activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-B. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria. © 2010 USCAP, Inc All rights reserved. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010 |
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/20.500.12110/paper_00236837_v90_n7_p1049_Salamone |
url |
http://hdl.handle.net/20.500.12110/paper_00236837_v90_n7_p1049_Salamone |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by/2.5/ar |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Lab. Invest. 2010;90(7):1049-1059 reponame:Biblioteca Digital (UBA-FCEN) instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN |
reponame_str |
Biblioteca Digital (UBA-FCEN) |
collection |
Biblioteca Digital (UBA-FCEN) |
instname_str |
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
instacron_str |
UBA-FCEN |
institution |
UBA-FCEN |
repository.name.fl_str_mv |
Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
repository.mail.fl_str_mv |
ana@bl.fcen.uba.ar |
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1844618737628479488 |
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13.070432 |