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.
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Authors | Ling-Feng Wang, Chen-Yu Chien, Yi-Hsin Yang, Tzyh-Chyuan Hour, Sheau-Fang Yang, Hau-Ren Chen, Ke-Li Tsai, Jenq-Yuh Ko, Jeff Yi-Fu Chen |
Journal | Rhinology
(Rhinology)
Vol. 53
Issue 3
Pg. 270-6
(09 2015)
ISSN: 0300-0729 [Print] Netherlands |
PMID | 26363168
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MAP1LC3A protein, human
- Microtubule-Associated Proteins
- Cyclooxygenase 2
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Topics |
- Autophagy
(physiology)
- Case-Control Studies
- Cell Culture Techniques
- Cyclooxygenase 2
(metabolism)
- Fibroblasts
(physiology)
- Humans
- Microtubule-Associated Proteins
(metabolism)
- Nasal Polyps
(metabolism, pathology)
- Rhinitis
(etiology)
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