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 (2006). CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death. American journal of respiratory cell and molecular biology, 35(2), pp. 155-64. New York, N.Y.: American Lung Association 10.1165/rcmb.2005-0433OC
Full text not available from this repository. (Request a copy)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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Simon, Hans-Uwe |
ISSN: |
1044-1549 |
ISBN: |
16543604 |
Publisher: |
American Lung Association |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:48 |
Last Modified: |
05 Dec 2022 14:15 |
Publisher DOI: |
10.1165/rcmb.2005-0433OC |
PubMed ID: |
16543604 |
Web of Science ID: |
000239537500003 |
URI: |
https://boris.unibe.ch/id/eprint/20236 (FactScience: 3423) |