title: Supplementing defect in club cell secretory protein attenuates airway inflammation in COPD.
abstract: BACKGROUND
  Club cell secretory protein (CCSP) is a protective biomarker associated with annual decline in lung function. COPD progression results from an imbalance between injury and repair initially triggered by cigarette smoking.
  
  
  OBJECTIVE
  We investigated the effect of CCSP as a therapeutic strategy to restore the balance between injury and repair in COPD simultaneously, validating an ex vivo air-liquid interface (ALI) culture of human bronchial epithelial cells.
  
  
  METHODS
  Endobronchial biopsy specimens (EBBs) were obtained from 13 patients with COPD, eight smokers, and eight control subjects. Morphometric analysis of the initial EBBs was performed. ALI cultures derived from the same EBBs were exposed to cigarette smoke extract (CSE) with or without exogenous recombinant human CCSP (rhCCSP) supplementation. CCSP and IL-8 concentrations were assessed at steady state and after CSE exposure.
  
  
  RESULTS
  Morphometric analysis of the initial EBBs showed increased cell density but decreased immunostaining of CCSP+ cells in EBBs of patients with COPD (P = .03 vs control subjects). At steady state, lower CCSP (P = .04) and higher IL-8 levels (P < .0001) were found in COPD ALI epithelium. Exogenous rhCCSP supplementation dampened CSE-induced IL-8-release in patients with COPD and returned to levels similar to those of smokers and control subjects (P = .0001). A negative correlation was found between IL-8-release in ALI and CCSP+ cell density in initial biopsy specimens (P = .0073).
  
  
  CONCLUSIONS
  In vitro, rhCCSP exogenous supplementation can reverse CSE-induced IL-8 release in biopsy specimens from patients with COPD, indicating a potential use of this strategy in vivo.
authors.affiliation: Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier.
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Gamez
authors.affiliation: INSERM CNRS U1067 UMR7333, Aix Marseille Université, Marseille.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gras
authors.affiliation: Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Petit
authors.affiliation: Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier; INSERM U1046, Université Montpellier 1 et 2, Hôpital Arnaud de Villeneuve, CHU Montpellier, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Knabe
authors.affiliation: Département de l'Information Médicale, CHU Montpellier, Montpellier; UMR729 MISTEA, Montpellier SupAgro, Montpellier.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molinari
authors.affiliation: Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
authors.affiliation: INSERM CNRS U1067 UMR7333, Aix Marseille Université, Marseille; Département des Maladies Respiratoires, Hôpital Nord, AP-HM, Marseille.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.affiliation: Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, CHU Montpellier; INSERM U1046, Université Montpellier 1 et 2, Hôpital Arnaud de Villeneuve, CHU Montpellier, France. Electronic address: a-bourdin@chu-montpellier.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourdin
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D012907:Smoking / Q000009:adverse effects; D014598:Uteroglobin / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; D009538:Nicotine; D014598:Uteroglobin