title: Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pneumonology, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Plataki
authors.forename: Anastassios V
authors.initials: AV
authors.lastname: Koutsopoulos
authors.forename: Katherine
authors.initials: K
authors.lastname: Darivianaki
authors.forename: George
authors.initials: G
authors.lastname: Delides
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000097:blood; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000166:cytology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D015854:Up-Regulation / Q000502:physiology; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases