Oxidative stress induces unfolding protein response and inflammation in nasal polyposis

• Published in: Allergy (Copenhagen) 2012-03, Vol.67 (3), p.403-412
• Main Authors: Jeanson, L., Kelly, M., Coste, A., Guerrera, I. C., Fritsch, J., Nguyen-Khoa, T., Baudouin-Legros, M., Papon, J.-F., Zadigue, P., Prulière-Escabasse, V., Amselem, S., Escudier, E., Edelman, A.
• Format: Article
• Language: English
• Subjects: airways; Antioxidants; Antioxidants - pharmacology; Biochemical analysis; Biological and medical sciences; Calreticulin; Cell culture; Cells, Cultured; Dermatology; Endoplasmic Reticulum Chaperone BiP; Epithelial Cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Human health and pathology; Humans; Immunocytochemistry; Inflammation; Inflammation - immunology; Inflammatory diseases; Interleukin 8; Interleukin-8 - metabolism; Leukotriene B4; Leukotriene B4 - metabolism; Life Sciences; Mass spectroscopy; Medical sciences; Mitochondria; Mucosa; Nasal Mucosa; Nasal Mucosa - cytology; Nasal Mucosa - immunology; Nasal Polyps; Nasal Polyps - immunology; Nasal Polyps - physiopathology; Nose; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Oxidative Stress; polyposis; Polyps; Protein disulfide-isomerase; Protein folding; Proteome; Proteomics; Pulmonology and respiratory tract; Redox properties; Respiratory tract; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Tissues and Organs; Tumors; Unfolded Protein Response
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2011.02769.x

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.