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Laboratory and Animal Investigations |

Expression of Apoptotic and Antiapoptotic Markers in Epithelial Cells in Idiopathic Pulmonary Fibrosis*

Maria Plataki, MD; Anastassios V. Koutsopoulos, MD; Katherine Darivianaki, BS; George Delides, MD, PhD; Nikolaos M. Siafakas, MD, PhD, FCCP; Demosthenes Bouros, MD, FCCP
Author and Funding Information

*From the Departments of Pneumonology (Drs. Plataki and Siafakas) and Pathology (Drs. Koutsopoulos and Delides, and Ms. Darivianaki), Medical School, University of Crete, Heraklion, Crete, Greece; and the Department of Pneumonology (Dr. Bouros), Medical School, University of Thrace, Alexandroupolis, Thrace, Greece.

Correspondence to: Demosthenes Bouros, MD, FCCP, Professor of Pneumonology, Medical School University of Thrace, University General Hospital, Alexandroupolis 68100, Greece; e-mail: bouros@med.duth.gr



Chest. 2005;127(1):266-274. doi:10.1378/chest.127.1.266
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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, bcl-2, bax, and caspase-3 in association with DNA strand breaks in bronchial and alveolar epithelial cells in lung specimens from IPF patients and control subjects.

Patients and methods: We examined by immunohistochemistry the expression of p53, p21, bax, bcl-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 IPF 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 IPF patients and only in one control subject. The expression of p53, p21, bax, and caspase-3 was up-regulated in IPF patients compared to control subjects. Bcl-2 was expressed less in IPF patients than in control subjects.

Conclusions: These results confirm that apoptotic hyperplastic epithelial cells are present in patients with IPF and that the expression of p53, p21, bax, and caspase-3 appears to be up-regulated and that of bcl-2 down-regulated in these cells. The increased expression of proapoptotic molecules in epithelial cells in IPF may be involved in the inadequate and delayed reepithelialization, which in turn contributes to fibroblast proliferation.

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