Oxidative stress induces unfolding protein response and inflammation in nasal polyposis.
Allergy
; 67(3): 403-12, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22188019
ABSTRACT
BACKGROUND:
Nasal polyposis, a chronic inflammatory disease affecting the upper airways, is a valuable and accessible model to investigate the mechanisms underlying chronic inflammation. The main objective of this study was to investigate a potential involvement of the unfolded protein response (UPR) in the context of oxidative stress and inflammation in nasal epithelial cells from nasal polyps (NP).METHODS:
Epithelial cells from NP (n = 20) and normal mucosa (Controls, n = 15) in primary culture were analyzed by global proteomic approach and cell biology techniques for the glucose-regulated protein 78 (GRP78), the spliced X-box-binding protein 1 (sXBP-1), the glucose-regulated protein 94 (GRP94), and the calreticulin (immunoblot, mass spectrometry, immunocytochemistry).RESULTS:
Proteomics analysis of human nasal epithelial cells in culture revealed the activation of the unfolded protein response in NP. Systematic cell biology and biochemical analysis of two markers (GRP78, sXBP-1) in the presence and absence of oxidative stress in NP showed a susceptibility of the unfolded protein response to oxidative stress compared to controls at least partially linked to an abnormal redox state of the protein disulfide-isomerase 4. This unfolded protein response was correlated with mitochondrial depolarization and secretion of interleukin 8 (IL-8) and leukotriene B4 (LTB4) and was prevented by mitochondrial antioxidant.CONCLUSIONS:
We show the existence of UPR in nasal epithelial cells that is linked to oxidative stress leading to IL-8 and LTB4 secretions. These mechanisms may participate in chronic inflammation in nasal polyposis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pólipos Nasais
/
Estresse Oxidativo
/
Células Epiteliais
/
Resposta a Proteínas não Dobradas
/
Inflamação
/
Mucosa Nasal
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Allergy
Ano de publicação:
2012
Tipo de documento:
Article