Convergent sets of data from In Vivo and In Vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis

Francesco Cappello, Gaetano Caramori, Claudia Campanella, Chiara Vicari, Isabella Gnemmi, Andrea Zanini, Antonio Spanevello, Armando Capelli, Giampiero la Rocca, Rita Anzalone, Fabio Bucchieri, Silvestro Ennio D'Anna, Fabio L M Ricciardolo, Paola Brun, Bruno Balbi, Mauro Carone, Giovanni Zummo, Everly Conway de Macario, Alberto J L Macario, Antonino Di Stefano

Research output: Contribution to journalArticle

37 Citations (Scopus)

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. Methods and 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.

Original languageEnglish
Article numbere28200
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 28 2011

Fingerprint

Pulmonary diseases
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
pathogenesis
neutrophils
epithelial cells
Neutrophils
Oxidative stress
Epithelial Cells
Heat-Shock Proteins
heat shock proteins
Oxidative Stress
oxidative stress
inflammation
methodology
Disease control
Inflammation
Biopsy
lung function
Cell death

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Convergent sets of data from In Vivo and In Vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis. / Cappello, Francesco; Caramori, Gaetano; Campanella, Claudia; Vicari, Chiara; Gnemmi, Isabella; Zanini, Andrea; Spanevello, Antonio; Capelli, Armando; la Rocca, Giampiero; Anzalone, Rita; Bucchieri, Fabio; D'Anna, Silvestro Ennio; Ricciardolo, Fabio L M; Brun, Paola; Balbi, Bruno; Carone, Mauro; Zummo, Giovanni; de Macario, Everly Conway; Macario, Alberto J L; Di Stefano, Antonino.

In: PLoS One, Vol. 6, No. 11, e28200, 28.11.2011.

Research output: Contribution to journalArticle

Cappello, F, Caramori, G, Campanella, C, Vicari, C, Gnemmi, I, Zanini, A, Spanevello, A, Capelli, A, la Rocca, G, Anzalone, R, Bucchieri, F, D'Anna, SE, Ricciardolo, FLM, Brun, P, Balbi, B, Carone, M, Zummo, G, de Macario, EC, Macario, AJL & Di Stefano, A 2011, 'Convergent sets of data from In Vivo and In Vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis', PLoS One, vol. 6, no. 11, e28200. https://doi.org/10.1371/journal.pone.0028200
Cappello, Francesco ; Caramori, Gaetano ; Campanella, Claudia ; Vicari, Chiara ; Gnemmi, Isabella ; Zanini, Andrea ; Spanevello, Antonio ; Capelli, Armando ; la Rocca, Giampiero ; Anzalone, Rita ; Bucchieri, Fabio ; D'Anna, Silvestro Ennio ; Ricciardolo, Fabio L M ; Brun, Paola ; Balbi, Bruno ; Carone, Mauro ; Zummo, Giovanni ; de Macario, Everly Conway ; Macario, Alberto J L ; Di Stefano, Antonino. / Convergent sets of data from In Vivo and In Vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis. In: PLoS One. 2011 ; Vol. 6, No. 11.
@article{e5f1a538503544f0a13bc7732829199c,
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. Methods and 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.",
author = "Francesco Cappello and Gaetano Caramori and Claudia Campanella and Chiara Vicari and Isabella Gnemmi and Andrea Zanini and Antonio Spanevello and Armando Capelli and {la Rocca}, Giampiero and Rita Anzalone and Fabio Bucchieri and D'Anna, {Silvestro Ennio} and Ricciardolo, {Fabio L M} and Paola Brun and Bruno Balbi and Mauro Carone and Giovanni Zummo and {de Macario}, {Everly Conway} and Macario, {Alberto J L} and {Di Stefano}, Antonino",
year = "2011",
month = "11",
day = "28",
doi = "10.1371/journal.pone.0028200",
language = "English",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Convergent sets of data from In Vivo and In Vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis

AU - Cappello, Francesco

AU - Caramori, Gaetano

AU - Campanella, Claudia

AU - Vicari, Chiara

AU - Gnemmi, Isabella

AU - Zanini, Andrea

AU - Spanevello, Antonio

AU - Capelli, Armando

AU - la Rocca, Giampiero

AU - Anzalone, Rita

AU - Bucchieri, Fabio

AU - D'Anna, Silvestro Ennio

AU - Ricciardolo, Fabio L M

AU - Brun, Paola

AU - Balbi, Bruno

AU - Carone, Mauro

AU - Zummo, Giovanni

AU - de Macario, Everly Conway

AU - Macario, Alberto J L

AU - Di Stefano, Antonino

PY - 2011/11/28

Y1 - 2011/11/28

N2 - 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. Methods and 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.

AB - 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. Methods and 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.

UR - http://www.scopus.com/inward/record.url?scp=82155182139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82155182139&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0028200

DO - 10.1371/journal.pone.0028200

M3 - Article

C2 - 22140545

AN - SCOPUS:82155182139

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e28200

ER -