Ceramide expression and cell homeostasis in chronic obstructive pulmonary disease

Abstract

Background: Increased expression of ceramide has been detected in emphysema. Ceramide promotes autophagy and apoptosis, which concur with cellular homeostasis. Objectives: To determine whether ceramide expression is associated with the development of chronic obstructive pulmonary disease (COPD) and with altered cellular homeostasis in lung parenchyma. Methods: We studied 10 subjects with severe COPD, 13 with mild/moderate COPD, 11 with idiopathic pulmonary fibrosis (IPF), 12 non-COPD smokers, and 11 nonsmoking controls. The immunoreactivity for ceramide along with markers of autophagy (LC3B), apoptosis (cleaved caspase-3), and cell proliferation (MIB1) was quantified in alveolar walls. Results: Ceramide expression was increased in COPD patients compared with control smokers and was related to the impairment of gas exchange but not to the degree of airflow limitation. In COPD, an important activation of apoptosis and autophagy pathways was observed, particularly in patients with severe disease, that was not counterbalanced by cell proliferation. Upregulation of ceramide was observed even in subjects with IPF in whom activation of apoptosis and autophagy was negligible and cell proliferation was instead the most prominent feature. Conclusions: Ceramide expression, which is increased in COPD and even more so in IPF, appears to be neither specific nor related to COPD severity, probably representing a broader marker of lung damage. In contrast, apoptosis and autophagy are characteristics of the COPD pathology, particularly in its most severe stage. Copyright © 2012 S. Karger AG, Basel.