Edited by: Wytske Fokkens
Oxidative stress induces unfolding protein response and inflammation in nasal polyposis
Article first published online: 22 DEC 2011
© 2011 John Wiley & Sons A/S
Volume 67, Issue 3, pages 403–412, March 2012
How to Cite
- Issue published online: 11 FEB 2012
- Article first published online: 22 DEC 2011
- Manuscript Accepted: 17 NOV 2011
- Agence Nationale pour la Recherche. Grant Number: 05-MRAR-02201
- European Community: Life Sciences and Health Grant. Grant Number: LSHG-CT-2005-512044
- French Foundation for Cystic Fibrosis
- Chancellerie des Université
- oxidative stress;
- unfolded protein response.
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).
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).
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.
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.