Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: A novel insight into the inflammation mechanism
Journal
Rhinology
Journal Volume
53
Journal Issue
3
Pages
270-276
Date Issued
2015
Author(s)
Abstract
Background: Nasal polyposis is characterised by persistent inflammation of the upper airways. Autophagy has been implicated in many chronic inflammatory diseases. Whether autophagy plays a role in nasal polyp (NP) inflammation is completely unknown and deserves investigation. Methods: LC3 and COX-2 expression, the common autophagy and inflammation indicators, respectively, was analysed by immunoblotting in fresh tissues of NP and control nasal mucosa (NM). Primary cultures of NP-derived fibroblasts (NPDFs) and NMDFs were established for in vitro studies. Autophagy was induced by amino acid starvation and LC3 ectopic overexpression or inhibited by 3-methyladenine in the fibroblasts. Inflammation was induced by IL1-β and TNF-α. LC3 and COX-2 expression was confirmed in NP specimens by immunohistochemistry. Results: LC3 expression was decreased while COX-2 expression was significantly increased in fresh NP tissues compared with the NM control. In NMDFs and NPDFs, autophagy induction by starvation and LC3 overexpression downregulated COX-2 expression. Conversely, autophagy inhibition by 3-methyladenine enhanced COX-2 expression. However, IL1-β and TNF-α had no effect on autophagy. Immunohistochemical studies on the NP specimens showed that most displayed low LC3 expression, whereas COX-2 was highly expressed in >50% of the specimens. Examination of two consecutive NP sections from the same tissue blocks revealed a negative correlation between LC3 and COX-2 expression. Conclusion: Autophagy is deficient in NP tissues and COX-2 is negatively regulated by autophagy in NP-derived fibroblasts. Since COX-2 is essential for the production of pro-inflammatory mediators, this study might help interpret persistent mucosal inflammation in NP. Attenuation of inflammation by restoring autophagy might be a therapeutic strategy for treating NP. ? 2015 AMC. All rights reserved.
Subjects
Autophagy; COX-2; Inflammation; LC3; Nasal polyp
SDGs
Other Subjects
cyclooxygenase 2; light chain 3, human; microtubule associated protein; autophagy; case control study; culture technique; fibroblast; human; metabolism; nose polyp; pathology; physiology; rhinitis; Autophagy; Case-Control Studies; Cell Culture Techniques; Cyclooxygenase 2; Fibroblasts; Humans; Microtubule-Associated Proteins; Nasal Polyps; Rhinitis
Publisher
AMC
Type
journal article