title: Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: a novel insight into the inflammation mechanism.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.forename: Ling-Feng
authors.initials: LF
authors.lastname: Wang
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Chien
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Yang
authors.forename: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Hau-Ren
authors.initials: HR
authors.lastname: Chen
authors.forename: Ke-Li
authors.initials: KL
authors.lastname: Tsai
authors.forename: Jenq-Yuh
authors.initials: JY
authors.lastname: Ko
authors.forename: Jeff Yi-Fu
authors.initials: JY
authors.lastname: Chen
mesh_terms: D001343:Autophagy / Q000502:physiology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis / Q000209:etiology*
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D051546:Cyclooxygenase 2