RGD Reference Report - Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis. - Rat Genome Database

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Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.

Authors: Cappello, F  Caramori, G  Campanella, C  Vicari, C  Gnemmi, I  Zanini, A  Spanevello, A  Capelli, A  Rocca, GL  Anzalone, R  Bucchieri, F  D'Anna, SE  Ricciardolo, FL  Brun, P  Balbi, B  Carone, M  Zummo, G  Macario, EC  Macario, AJ  Stefano, AD 
Citation: Cappello F, etal., PLoS One. 2011;6(11):e28200. Epub 2011 Nov 28.
RGD ID: 5688781
Pubmed: PMID:22140545   (View Abstract at PubMed)
PMCID: PMC3225395   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0028200   (Journal Full-text)

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 HO. 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 HO 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chronic obstructive pulmonary disease no_associationIEP 5688781protein:increased expression:bronchial mucosa (human)RGD 
chronic obstructive pulmonary disease no_associationISOHSPA4 (Homo sapiens)5688781; 5688781protein:increased expression:bronchial mucosa (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa4  (heat shock protein family A (Hsp70) member 4)

Genes (Mus musculus)
Hspa4  (heat shock protein 4)

Genes (Homo sapiens)
HSPA4  (heat shock protein family A (Hsp70) member 4)


Additional Information