Published ahead of print on March 16, 2006, doi:10.1165/rcmb.2005-0433OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0433OC CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death Department of Medicine, Pneumology, Physiology, and Human Nutrition; Department of Experimental Medicine, Section of Human Anatomy, Università di Palermo, Palermo; Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; Division of Infection, Inflammation, and Repair, University of Southampton, United Kingdom; and Department of Pharmacology, University of Bern, Bern, Switzerland Correspondence and requests for reprints should be addressed to Anna Maria Merendino, Ph.D., Dipartimento di Medicina, Pneumologia, Fisiologia e Nutrizione Umana, Universita' di Palermo, Ospedale "V, Cervello", Via Trabucco 180, 90146 Palermo, Italy. E-mail: annameren{at}yahoo.it
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-
Key Words: activator protein–1 • apoptosis • CD40 • NF- This article has been cited by other articles:
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B 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. 
