CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death.

2.50
Hdl Handle:
http://hdl.handle.net/10146/64977
Title:
CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death.
Authors:
Merendino, Anna M.; Bucchieri, Fabio; Gagliardo, Rosalia; Daryadel, Arezoo; Pompeo, Flora; Chiappara, Giuseppina; Santagata, Roberta; Bellia, Vincenzo; David, Sabrina; Farina, Felicia; Davies, Donna E.; Simon, Hans-Uwe; Vignola, Antonio M.
Abstract:
CD40 and its ligand regulate pleiotropic biological responses, including cell proliferation, differentiation, and apoptosis. In many inflammatory lung diseases, tissue damage by environmental or endogenous oxidants plays a major role in disease pathogenesis. As the epithelial barrier is a major target for these oxidants, we postulated that CD40, the expression of which is increased in asthma, plays a role in the regulation of apoptosis of bronchial epithelial cells exposed to oxidants. Using 16HBE 14o- cells exposed to oxidant stress, we found that ligation of CD40 (induced by G28-5 monoclonal antibodies) enhanced cell survival and increased the number of cells in G2/M (interphase between DNA synthesis and mitosis) of the cell cycle. This was associated with NF-kappaB and activator protein-1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress-induced apoptosis was found to be caspase- and calpain-independent implicating CD40 ligation as a regulator of caspase-independent cell death. This was confirmed by the demonstration that CD40 ligation prevented mitochondrial release and nuclear translocation of apoptosis inducing factor. In conclusion, we demonstrate a novel role for CD40 as a regulator of epithelial cell survival against oxidant stress. Furthermore, we have identified, for the first time, an endogenous inhibitory pathway of caspase-independent cell death.
Citation:
Am. J. Respir. Cell Mol. Biol. 2006, 35 (2):155-164
Journal:
American journal of respiratory cell and molecular biology
Issue Date:
Aug-2006
URI:
http://hdl.handle.net/10146/64977
DOI:
10.1165/rcmb.2005-0433OC
PubMed ID:
16543604
Additional Links:
http://ajrcmb.atsjournals.org/cgi/content/full/35/2/155
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide;Antigens,CD40;Apoptosis;Bronchi;cytology;Caspases;Cell Cycle;Cell Death;Cell Line,Transformed;Cell Survival;Cell Transformation,Viral;Cytoprotection;drug effects;Epithelial Cells;Humans;Italy;mechanisms of carcinogenesis;metabolism;Oxidants;pharmacology;physiology;Research;Simian virus 40;toxicity;Transcription Factor AP-1.
ISSN:
1044-1549
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorMerendino, Anna M.-
dc.contributor.authorBucchieri, Fabio-
dc.contributor.authorGagliardo, Rosalia-
dc.contributor.authorDaryadel, Arezoo-
dc.contributor.authorPompeo, Flora-
dc.contributor.authorChiappara, Giuseppina-
dc.contributor.authorSantagata, Roberta-
dc.contributor.authorBellia, Vincenzo-
dc.contributor.authorDavid, Sabrina-
dc.contributor.authorFarina, Felicia-
dc.contributor.authorDavies, Donna E.-
dc.contributor.authorSimon, Hans-Uwe-
dc.contributor.authorVignola, Antonio M.-
dc.date.accessioned2009-04-15T12:19:11Z-
dc.date.available2009-04-15T12:19:11Z-
dc.date.issued2006-08-
dc.identifier.citationAm. J. Respir. Cell Mol. Biol. 2006, 35 (2):155-164en
dc.identifier.issn1044-1549-
dc.identifier.pmid16543604-
dc.identifier.doi10.1165/rcmb.2005-0433OC-
dc.identifier.urihttp://hdl.handle.net/10146/64977-
dc.descriptionKEYWORDS CLASSIFICATION: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide;Antigens,CD40;Apoptosis;Bronchi;cytology;Caspases;Cell Cycle;Cell Death;Cell Line,Transformed;Cell Survival;Cell Transformation,Viral;Cytoprotection;drug effects;Epithelial Cells;Humans;Italy;mechanisms of carcinogenesis;metabolism;Oxidants;pharmacology;physiology;Research;Simian virus 40;toxicity;Transcription Factor AP-1.en
dc.description.abstractCD40 and its ligand regulate pleiotropic biological responses, including cell proliferation, differentiation, and apoptosis. In many inflammatory lung diseases, tissue damage by environmental or endogenous oxidants plays a major role in disease pathogenesis. As the epithelial barrier is a major target for these oxidants, we postulated that CD40, the expression of which is increased in asthma, plays a role in the regulation of apoptosis of bronchial epithelial cells exposed to oxidants. Using 16HBE 14o- cells exposed to oxidant stress, we found that ligation of CD40 (induced by G28-5 monoclonal antibodies) enhanced cell survival and increased the number of cells in G2/M (interphase between DNA synthesis and mitosis) of the cell cycle. This was associated with NF-kappaB and activator protein-1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress-induced apoptosis was found to be caspase- and calpain-independent implicating CD40 ligation as a regulator of caspase-independent cell death. This was confirmed by the demonstration that CD40 ligation prevented mitochondrial release and nuclear translocation of apoptosis inducing factor. In conclusion, we demonstrate a novel role for CD40 as a regulator of epithelial cell survival against oxidant stress. Furthermore, we have identified, for the first time, an endogenous inhibitory pathway of caspase-independent cell death.en
dc.language.isoenen
dc.relation.urlhttp://ajrcmb.atsjournals.org/cgi/content/full/35/2/155en
dc.subjectActivator protein–1en
dc.subjectApoptosisen
dc.subjectCD40en
dc.subjectNF-Ben
dc.subjectOxidant stressen
dc.subject.mesh7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide-
dc.subject.meshAntigens, CD40-
dc.subject.meshApoptosis-
dc.subject.meshBronchi-
dc.subject.meshCaspases-
dc.subject.meshCell Cycle-
dc.subject.meshCell Death-
dc.subject.meshCell Line, Transformed-
dc.subject.meshCell Survival-
dc.subject.meshCell Transformation, Viral-
dc.subject.meshCytoprotection-
dc.subject.meshEpithelial Cells-
dc.subject.meshHumans-
dc.subject.meshOxidants-
dc.subject.meshSimian virus 40-
dc.subject.meshTranscription Factor AP-1-
dc.titleCD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death.en
dc.typeArticleen
dc.identifier.journalAmerican journal of respiratory cell and molecular biologyen
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