title: Altered expression of p21, activated caspase-3, and PCNA in bronchiolar epithelium of smokers with and without chronic obstructive pulmonary disease.
abstract: ABSTRACT Background: The cyclin-dependent kinase inhibitor p21CIP1/WAF1 is involved in cell-cycle growth arrest due to cell stressors, such as cigarette smoke. The role of p21 in cell apoptosis is controversial as it exerts pro- or antiapoptotic effects in different cells. In the present study, we investigated whether, in the epithelium of small airways of smokers with and without COPD, altered p21 expression is associated with an imbalance between proliferation and apoptosis.
  
  
  OBJECTIVE
  The expression of specific molecules involved in the regulation of apoptosis, such as activated caspase-3 and cytoplasmic p21, cell quiescence (G0) or proliferation markers such as Ki67 and PCNA, and cell-cycle markers such as the nuclear p21, was assessed in the small airway (bronchiolar) epithelium of smokers with and without COPD and in nonsmoker non-COPD subjects.
  
  
  RESULTS
  In smokers with and without COPD, we found an increase of cytoplasmic nuclear p21 and activated caspase-3 expression. By contrast, we verified in all the studied groups a similar low expression of the proliferation marker Ki67 and a reduced expression of PCNA in smokers and smokers with COPD.
  
  
  CONCLUSIONS
  In the small airway epithelium, cytoplasmic p21 correlating with increased activated caspase-3 expression might play a proapoptotic role. Furthermore, p21 alteration may be associated with the inhibition of tissue repair in smokers and smokers with COPD as confirmed by the low expression of proliferation markers such as PCNA. All these events may play a role in the permanent cellular damage leading to the destruction of bronchiolar tissue.
authors: 1Istituto di Biomedicina e Immunologia Molecolare (I.B.I.M.), Commessa di Immunopatologia e Farmacologia Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche , Palermo , Italy.
authors: Giuseppina
authors: G
authors: Chiappara
authors: Mark
authors: M
authors: Gjomarkaj
authors: Serafina
authors: S
authors: Sciarrino
authors: Patrizio
authors: P
authors: Vitulo
authors: Loredana
authors: L
authors: Pipitone
authors: Elisabetta
authors: E
authors: Pace
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001980:Bronchi / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012906:Smoke; D012907:Smoking / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D012906:Smoke; D053148:Caspase 3
keywords: cigarette smoke; distal airways; epithelium; injury; lung