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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\u2212 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-\u03baB and activator protein\u20131 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress\u2013induced 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.<\/jats:p>","DOI":"10.1165\/rcmb.2005-0433oc","type":"journal-article","created":{"date-parts":[[2006,3,16]],"date-time":"2006-03-16T20:45:19Z","timestamp":1142541919000},"page":"155-164","source":"Crossref","is-referenced-by-count":12,"title":["CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death"],"prefix":"10.1093","volume":"35","author":[{"given":"Anna M.","family":"Merendino","sequence":"first","affiliation":[{"name":"Department of Medicine, Pneumology, Physiology, and Human Nutrition; Department of Experimental Medicine, Section of Human Anatomy, Universit\u00e0 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 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