2-DE reveals proteasome impairment in 16-HBE cells after LPS and CSE exposure

Chronic obstructive pulmonary disease (COPD) is characterized by progressive, irreversible airflow limitation. The primary risk factor for COPD is tobacco smoking and recurrent infections. A better understanding of the pathways by which cigarette smoke and recurrent infection might contribute to the development of COPD may enhance the opportunities for disease treatments. The aim of this study was to detect different protein patterns in immortalized normal bronchial epithelial cell line (16-HBE) stimulated with cigarette smoke extract (CSE) and lipopolysaccharide (LPS), a constituent of the outer wall of gram-negative bacteria, alone and/or in combination, by two-dimensional electrophoresis (2DE) analysis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We detected differentially expressed proteins. Among them, six proteins are related to stress response. Bioinformatic analysis suggested that this dysregulation could affect proteasome activity. In our experimental model, Proteasome activator complex subunit 2 (PSME2), a subunit of proteasome activator PA28 (11S), is down-regulated after the exposure to CSE combined with LPS. The proteasome is involved in many essential cellular functions and its main role is to degrade unnecessary or damaged protein by proteolysis. In chronic obstructive pulmonary disease (COPD), pulmonary proteasome expression and activity are downregulated and inversely correlate with lung function (1). This suggests that proteasome dysfunction can be regarded as a new pathomechanism for chronic lung diseases, awaiting further therapeutic exploration in the future.