title: Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.
abstract: BACKGROUND
  It is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.
  
  
  RESULTS
  Bronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between the number of neutrophils and Hsp60 levels. Double-immunostaining showed that Hsp60-positive neutrophils were significantly increased in COPD patients. We then investigated in vitro the effect on Hsp60 expression in bronchial epithelial cells (16HBE) caused by oxidative stress, a hallmark of COPD mucosa, which we induced with H₂O₂. This stressor determined increased levels of Hsp60 through a gene up-regulation mechanism involving NFkB-p65. Release of Hsp60 in the extracellular medium by the bronchial epithelial cells was also increased after H₂O₂ treatment in the absence of cell death.
  
  
  CONCLUSIONS
  This is the first report clearly pointing to participation of Hsps, particularly Hsp60, in COPD pathogenesis. Hsp60 induction by NFkB-p65 and its release by epithelial cells after oxidative stress can have a role in maintaining inflammation, e.g., by stimulating neutrophils activity. The data open new scenarios that might help in designing efficacious anti-inflammatory therapies centered on Hsp60 and applicable to COPD.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Anatomia Umana, Università degli Studi di Palermo, Palermo, Italy. francapp@hotmail.com
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.forename: Claudia
authors.initials: C
authors.lastname: Campanella
authors.forename: Chiara
authors.initials: C
authors.lastname: Vicari
authors.forename: Isabella
authors.initials: I
authors.lastname: Gnemmi
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanini
authors.forename: Antonio
authors.initials: A
authors.lastname: Spanevello
authors.forename: Armando
authors.initials: A
authors.lastname: Capelli
authors.forename: Giampiero
authors.initials: G
authors.lastname: La Rocca
authors.forename: Rita
authors.initials: R
authors.lastname: Anzalone
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Silvestro Ennio
authors.initials: SE
authors.lastname: D'Anna
authors.forename: Fabio L M
authors.initials: FL
authors.lastname: Ricciardolo
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Bruno
authors.initials: B
authors.lastname: Balbi
authors.forename: Mauro
authors.initials: M
authors.lastname: Carone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zummo
authors.forename: Everly
authors.initials: E
authors.lastname: Conway de Macario
authors.forename: Alberto J L
authors.initials: AJ
authors.lastname: Macario
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Stefano
mesh_terms: D000368:Aged; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001980:Bronchi / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018834:Chaperonin 60; D018836:Inflammation Mediators; D012333:RNA, Messenger; D051996:Transcription Factor RelA