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.
journal_name
Chestjournal_title
Chestauthors
Gamez AS,Gras D,Petit A,Knabe L,Molinari N,Vachier I,Chanez P,Bourdin Adoi
10.1378/chest.14-1174subject
Has Abstractpub_date
2015-06-01 00:00:00pages
1467-1476issue
6eissn
0012-3692issn
1931-3543pii
S0012-3692(15)37201-9journal_volume
147pub_type
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