Flagellin delays spontaneous human neutrophil apoptosis

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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 modu...

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Autores principales:	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.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2010
Materias:	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 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 immunoglobulin enhancer binding protein myeloid cell leukemia sequence 1 protein protein bcl 2 article bacterium mutant cell survival controlled study cytokine production enzyme phosphorylation flow cytometry fluorescence microscopy Helicobacter pylori human human cell leukocyte activation 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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00236837_v90_n7_p1049_Salamone
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_00236837_v90_n7_p1049_Salamone
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
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
spellingShingle	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 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. Flagellin delays spontaneous human neutrophil apoptosis
topic_facet	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
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.
format	Artículo Artículo publishedVersion
author	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_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_sort	Salamone, G.V.
title	Flagellin delays spontaneous human neutrophil apoptosis
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
publishDate	2010
url	http://hdl.handle.net/20.500.12110/paper_00236837_v90_n7_p1049_Salamone
work_keys_str_mv	AT salamonegv flagellindelaysspontaneoushumanneutrophilapoptosis AT petraccay flagellindelaysspontaneoushumanneutrophilapoptosis AT bassjif flagellindelaysspontaneoushumanneutrophilapoptosis AT rumbom flagellindelaysspontaneoushumanneutrophilapoptosis AT nahmodka flagellindelaysspontaneoushumanneutrophilapoptosis AT gabelloniml flagellindelaysspontaneoushumanneutrophilapoptosis AT vermeulenme flagellindelaysspontaneoushumanneutrophilapoptosis AT matteomj flagellindelaysspontaneoushumanneutrophilapoptosis AT geffnerjr flagellindelaysspontaneoushumanneutrophilapoptosis AT trevanias flagellindelaysspontaneoushumanneutrophilapoptosis
_version_	1769810221983596544
spelling	paperaa:paper_00236837_v90_n7_p1049_Salamone2023-06-12T16:44:54Z Flagellin delays spontaneous human neutrophil apoptosis Lab. Invest. 2010;90(7):1049-1059 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. 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 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. 2010 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00236837_v90_n7_p1049_Salamone

Flagellin delays spontaneous human neutrophil apoptosis

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