Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis

Study objective: Idiopathic pulmonary fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. A common feature is the presence of microscopic areas of epithelial cell dropout. Increased apoptosis of these cells could elucidate the speculative pathogenesis of the disease. Therefore, the aim of our study was to examine the expression of p53, p21, bcI-2, bax, and caspase-3 in association with DNA strand breaks in bronchial and alveolar epithelial cells in lung specimens from OF patients and control subjects. Patients and methods: We examined by immunohistochemistry the expression of p53, p21, bax, bcI-2, and caspase-3 in association with DNA strand breaks detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) in bronchial and alveolar epithelial cells in lung specimens taken by biopsy in 12 OF patients and 10 control subjects. An independent tissue evaluation by two pathologists graded semiquantatively the degree of staining present. Results: TUNEL was positive in epithelial cells in all OF patients and only in one control subject. The expression of p53, p21, bax, and caspase-3 was up-regulated in OF patients compared to control subjects. BcI-2 was expressed less in OF patients than in control subjects. Conclusions: These results confirm that apoptotic hyperplastic epithelial cells are present in patients with OF and that the expression of p53, p21, bax, and caspase-3 appears to be up-regulated and that of bcI-2 down-regulated in these cells. The increased expression of proapoptotic molecules in epithelial cells in OF may be involved in the inadequate and delayed reepithelialization, which in turn contributes to fibroblast proliferation.