title: Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients.
abstract: BACKGROUND
  Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms.
  
  
  METHODS
  The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13).
  
  
  RESULTS
  In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter.
  
  
  CONCLUSIONS
  This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD.
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy. pace@ibim.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Marta Ida
authors.initials: MI
authors.lastname: Minervini
authors.forename: Patrizio
authors.initials: P
authors.lastname: Vitulo
authors.forename: Loredana
authors.initials: L
authors.lastname: Pipitone
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chiappara
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Montalbano
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000368:Aged; D001483:Base Sequence; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002460:Cell Line; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: C106641:DEFB4A protein, human; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023083:beta-Defensins