CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death

Felicia Farina, Sabrina David, Fabio Bucchieri, Vincenzo Bellia, Arezoo Daryadel, Roberta Santagata, Flora Pompeo, Anna Maria Merendino, Fabio Bucchieri, Rosalia Gagliardo, Giuseppina Chiappara, Vincenzo Bellia, Antonio M. Vignola, Felicia Farina, Sabrina David, Hans-Uwe Simon, Donna E. Davies, Anna Maria Merendino

Risultato della ricerca: Article

15 Citazioni (Scopus)

Abstract

CD40 and its ligand regulate pleiotropic biological responses, includingcell proliferation, differentiation, and apoptosis. In manyinflammatory lung diseases, tissue damage by environmental orendogenous oxidants plays a major role in disease pathogenesis.As the epithelial barrier is a major target for these oxidants, wepostulated that CD40, the expression of which is increased inasthma, plays a role in the regulation of apoptosis of bronchialepithelial cells exposed to oxidants. Using 16HBE 14o cells exposedto oxidant stress, we found that ligation of CD40 (inducedby G28-5 monoclonal antibodies) enhanced cell survival and increasedthe number of cells in G2/M (interphase between DNAsynthesis and mitosis) of the cell cycle. This was associated withNF- B and activator protein–1 activation and increased expressionof the inhibitor of apoptosis, c-IAP1. However, oxidant stress–inducedapoptosiswas found to be caspase- and calpain-independent implicatingCD40 ligation as a regulator of caspase-independent cell death.This was confirmed by the demonstration that CD40 ligation preventedmitochondrial release and nuclear translocation of apoptosisinducing factor. In conclusion, we demonstrate a novel role forCD40 as a regulator of epithelial cell survival against oxidant stress.Furthermore, we have identified, for the first time, an endogenousinhibitory pathway of caspase-independent cell death.
Lingua originaleEnglish
pagine (da-a)155-164
Numero di pagine10
RivistaAmerican Journal of Respiratory Cell and Molecular Biology
Volume35(2)
Stato di pubblicazionePublished - 2006

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Cell death
Caspases
Oxidants
Ligation
Cell Death
Epithelium
Apoptosis
Cell Survival
Cells
Pulmonary diseases
CD40 Ligand
Calpain
Interphase
Mitosis
Lung Diseases
Cell Cycle
Demonstrations
Cell Count
Epithelial Cells
Chemical activation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cita questo

CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death. / Farina, Felicia; David, Sabrina; Bucchieri, Fabio; Bellia, Vincenzo; Daryadel, Arezoo; Santagata, Roberta; Pompeo, Flora; Merendino, Anna Maria; Bucchieri, Fabio; Gagliardo, Rosalia; Chiappara, Giuseppina; Bellia, Vincenzo; Vignola, Antonio M.; Farina, Felicia; David, Sabrina; Simon, Hans-Uwe; Davies, Donna E.; Merendino, Anna Maria.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 35(2), 2006, pag. 155-164.

Risultato della ricerca: Article

Farina, F, David, S, Bucchieri, F, Bellia, V, Daryadel, A, Santagata, R, Pompeo, F, Merendino, AM, Bucchieri, F, Gagliardo, R, Chiappara, G, Bellia, V, Vignola, AM, Farina, F, David, S, Simon, H-U, Davies, DE & Merendino, AM 2006, 'CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death', American Journal of Respiratory Cell and Molecular Biology, vol. 35(2), pagg. 155-164.
Farina, Felicia ; David, Sabrina ; Bucchieri, Fabio ; Bellia, Vincenzo ; Daryadel, Arezoo ; Santagata, Roberta ; Pompeo, Flora ; Merendino, Anna Maria ; Bucchieri, Fabio ; Gagliardo, Rosalia ; Chiappara, Giuseppina ; Bellia, Vincenzo ; Vignola, Antonio M. ; Farina, Felicia ; David, Sabrina ; Simon, Hans-Uwe ; Davies, Donna E. ; Merendino, Anna Maria. / CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death. In: American Journal of Respiratory Cell and Molecular Biology. 2006 ; Vol. 35(2). pagg. 155-164.
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abstract = "CD40 and its ligand regulate pleiotropic biological responses, includingcell proliferation, differentiation, and apoptosis. In manyinflammatory lung diseases, tissue damage by environmental orendogenous oxidants plays a major role in disease pathogenesis.As the epithelial barrier is a major target for these oxidants, wepostulated that CD40, the expression of which is increased inasthma, plays a role in the regulation of apoptosis of bronchialepithelial cells exposed to oxidants. Using 16HBE 14o cells exposedto oxidant stress, we found that ligation of CD40 (inducedby G28-5 monoclonal antibodies) enhanced cell survival and increasedthe number of cells in G2/M (interphase between DNAsynthesis and mitosis) of the cell cycle. This was associated withNF- B and activator protein–1 activation and increased expressionof the inhibitor of apoptosis, c-IAP1. However, oxidant stress–inducedapoptosiswas found to be caspase- and calpain-independent implicatingCD40 ligation as a regulator of caspase-independent cell death.This was confirmed by the demonstration that CD40 ligation preventedmitochondrial release and nuclear translocation of apoptosisinducing factor. In conclusion, we demonstrate a novel role forCD40 as a regulator of epithelial cell survival against oxidant stress.Furthermore, we have identified, for the first time, an endogenousinhibitory pathway of caspase-independent cell death.",
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author = "Felicia Farina and Sabrina David and Fabio Bucchieri and Vincenzo Bellia and Arezoo Daryadel and Roberta Santagata and Flora Pompeo and Merendino, {Anna Maria} and Fabio Bucchieri and Rosalia Gagliardo and Giuseppina Chiappara and Vincenzo Bellia and Vignola, {Antonio M.} and Felicia Farina and Sabrina David and Hans-Uwe Simon and Davies, {Donna E.} and Merendino, {Anna Maria}",
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T1 - CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death

AU - Farina, Felicia

AU - David, Sabrina

AU - Bucchieri, Fabio

AU - Bellia, Vincenzo

AU - Daryadel, Arezoo

AU - Santagata, Roberta

AU - Pompeo, Flora

AU - Merendino, Anna Maria

AU - Bucchieri, Fabio

AU - Gagliardo, Rosalia

AU - Chiappara, Giuseppina

AU - Bellia, Vincenzo

AU - Vignola, Antonio M.

AU - Farina, Felicia

AU - David, Sabrina

AU - Simon, Hans-Uwe

AU - Davies, Donna E.

AU - Merendino, Anna Maria

PY - 2006

Y1 - 2006

N2 - CD40 and its ligand regulate pleiotropic biological responses, includingcell proliferation, differentiation, and apoptosis. In manyinflammatory lung diseases, tissue damage by environmental orendogenous oxidants plays a major role in disease pathogenesis.As the epithelial barrier is a major target for these oxidants, wepostulated that CD40, the expression of which is increased inasthma, plays a role in the regulation of apoptosis of bronchialepithelial cells exposed to oxidants. Using 16HBE 14o cells exposedto oxidant stress, we found that ligation of CD40 (inducedby G28-5 monoclonal antibodies) enhanced cell survival and increasedthe number of cells in G2/M (interphase between DNAsynthesis and mitosis) of the cell cycle. This was associated withNF- B and activator protein–1 activation and increased expressionof the inhibitor of apoptosis, c-IAP1. However, oxidant stress–inducedapoptosiswas found to be caspase- and calpain-independent implicatingCD40 ligation as a regulator of caspase-independent cell death.This was confirmed by the demonstration that CD40 ligation preventedmitochondrial release and nuclear translocation of apoptosisinducing factor. In conclusion, we demonstrate a novel role forCD40 as a regulator of epithelial cell survival against oxidant stress.Furthermore, we have identified, for the first time, an endogenousinhibitory pathway of caspase-independent cell death.

AB - CD40 and its ligand regulate pleiotropic biological responses, includingcell proliferation, differentiation, and apoptosis. In manyinflammatory lung diseases, tissue damage by environmental orendogenous oxidants plays a major role in disease pathogenesis.As the epithelial barrier is a major target for these oxidants, wepostulated that CD40, the expression of which is increased inasthma, plays a role in the regulation of apoptosis of bronchialepithelial cells exposed to oxidants. Using 16HBE 14o cells exposedto oxidant stress, we found that ligation of CD40 (inducedby G28-5 monoclonal antibodies) enhanced cell survival and increasedthe number of cells in G2/M (interphase between DNAsynthesis and mitosis) of the cell cycle. This was associated withNF- B and activator protein–1 activation and increased expressionof the inhibitor of apoptosis, c-IAP1. However, oxidant stress–inducedapoptosiswas found to be caspase- and calpain-independent implicatingCD40 ligation as a regulator of caspase-independent cell death.This was confirmed by the demonstration that CD40 ligation preventedmitochondrial release and nuclear translocation of apoptosisinducing factor. In conclusion, we demonstrate a novel role forCD40 as a regulator of epithelial cell survival against oxidant stress.Furthermore, we have identified, for the first time, an endogenousinhibitory pathway of caspase-independent cell death.

KW - CD40

KW - NF- B

KW - activator protein–1

KW - apoptosis

KW - oxidant stress

UR - http://hdl.handle.net/10447/55703

M3 - Article

VL - 35(2)

SP - 155

EP - 164

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

ER -