Upregulation of TRAIL receptors and pro‐apoptotic factor Bax in emphysematous subjects

Emphysema is characterized by lung inflammation and pulmonary alveolar destruction. It has been shown that alveolar apoptosis is increased in emphysema. However, mechanisms that lead to this increase are still unknown. Our HYPOTHESIS is that the « TNF‐related apoptosis‐inducing ligand » (TRAIL) system and Bax are modulated in emphysema. TRAIL can induce apoptosis in a caspase‐dependent manner and can also induce the activation of the transcription factor NF‐kB. Bax is a pro‐apoptotic factor found in the cytoplasm and at the mitochondria outer membrane. Bax transcription can be induced by DNA damage. METHOD: Protein extracts of lung parenchyma of normal non‐smokers (NNS), normal smokers (NS), emphysematous smokers (ES), and emphysematous ex‐smokers (ExS) have been analysed by Western blot for the four receptors of TRAIL and Bax. RESULTS: We found that three of the four TRAIL receptors, two pro‐apoptotic receptors (TRAIL‐R1 and 2) and one anti‐apoptotic receptor (TRAIL‐R3), were significantly upregulated in ES and ExS. Bax was not detected in NNS, but was induced in NS and ExS, with a greater induction in ES. CONCLUSION: The TRAIL and Bax apoptotic pathways are upregulated in emphysema. Bax induction could be due to an increase of p53 activation caused by smoking and/or inflammation stresses. Effects of p53 and inflammatory mediators could explain TRAIL receptors upregulation in emphysema.