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

Vincenzo Bellia, Sabrina David, Fabio Bucchieri, Felicia Farina, Arezoo Daryadel, Roberta Santagata, Flora Pompeo, Anna Maria Merendino, Fabio Bucchieri, Rosalia Gagliardo, Giuseppina Chiappara, Vincenzo Bellia, Antonio M. Vignola, Felicia Farina, Sabrina David, Hans-Uwe Simon, Donna E. Davies, Anna Maria Merendino

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


CD40 and its ligand regulate pleiotropic biological responses, includingcell proliferation, differentiation, and apoptosis. In manyinflammatory lung diseases, tissue damage by environmental orendogenous oxidants plays a major role in disease pathogenesis.As the epithelial barrier is a major target for these oxidants, wepostulated that CD40, the expression of which is increased inasthma, plays a role in the regulation of apoptosis of bronchialepithelial cells exposed to oxidants. Using 16HBE 14o cells exposedto oxidant stress, we found that ligation of CD40 (inducedby G28-5 monoclonal antibodies) enhanced cell survival and increasedthe number of cells in G2/M (interphase between DNAsynthesis and mitosis) of the cell cycle. This was associated withNF- B and activator protein–1 activation and increased expressionof the inhibitor of apoptosis, c-IAP1. However, oxidant stress–inducedapoptosiswas found to be caspase- and calpain-independent implicatingCD40 ligation as a regulator of caspase-independent cell death.This was confirmed by the demonstration that CD40 ligation preventedmitochondrial release and nuclear translocation of apoptosisinducing factor. In conclusion, we demonstrate a novel role forCD40 as a regulator of epithelial cell survival against oxidant stress.Furthermore, we have identified, for the first time, an endogenousinhibitory pathway of caspase-independent cell death.
Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Publication statusPublished - 2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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