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- B and activator protein–1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress–induced apoptosiswas 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.

Merendino, A.M., Bucchieri, F., Gagliardo, R., Daryadel, A., Pompeo, F., Chiappara, G., et al. (2006). CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 35(2), 155-164 [10.1165/rcmb.2005-0433OC].

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

MERENDINO, Anna Maria;BUCCHIERI, Fabio;BELLIA, Vincenzo;DAVID, Sabrina;FARINA, Felicia;
2006-01-01

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- B and activator protein–1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress–induced apoptosiswas 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.
Merendino, A.M., Bucchieri, F., Gagliardo, R., Daryadel, A., Pompeo, F., Chiappara, G., et al. (2006). CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 35(2), 155-164 [10.1165/rcmb.2005-0433OC].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/55703
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